Daily Archives: September 14, 2022

At 44, Janet Waterhouse should have been the picture of health; a former Division I soccer player, she taught yoga, enjoyed running, and didnt drink alcohol. Despite her healthy and active lifestyle, over a span of decades she experienced a number of unexplained symptoms.

Her symptoms continued to worsen into her 20s when she began to sporadically lose function of her hands and experience severe bouts of vertigo. Most doctors attributed her symptoms to stress and anxiety. During this time, Waterhouse was seeing a pain management specialist, who was concerned enough about her worsening symptoms to run a blood test, where he found irregularly shaped blood cells, called acanthocytes.

A series of serendipitous referrals led Waterhouse to Ali Hamedani, an assistant professor of neurology and ophthalmology in the Perelman School of Medicine. Based on her symptoms and exam, he suspected a genetic condition called chronic progressive external ophthalmoplegia (CPEO) and referred her to Laynie Dratch, a certified genetic counselor in the Penn Neurogenetics Therapy Center, for genetic testing.

In May of 2022, Dratch gave Waterhouse what she had been chasing for decades: a diagnosis. When the genetic counselor told me they found the genetic mutation they were looking for, I cried for a solid five minutes out of relief, Waterhouse says.

Waterhouses case of CPEO was found to be caused by a variation on her RRM2B gene, which affects the mitochondria in her cells. While the condition is very rare and can sometimes take years to locate and diagnose, Hamedanis hunch about the gene mutation led them right to it.

Because little is known about CPEO, treatment options are limited. Most people would be discouraged by the uncertainty, she says, but it thrills me to get to be the blueprint. I get to show people how to live with this.

Launched in March 2020, the Penn Neurogenetics Therapy Center has a team of clinicians, nurses, genetic counselors, and clinical research staff who are devoted to the care of patients with inherited neurological disorders and to participating in clinical trials of novel gene and molecular therapies.

The programs mission is twofold: first, they utilize the expertise of clinicians and researchers throughout the department of Neurology and across Penn Medicine to achieve a genetic diagnosis for as many patients like Waterhouse as possible, creating a database of eligible patients for new treatments and clinical trials. Second, they work to establish clinical trials using novel gene and molecular therapies for patients with genetically-based neurological disorders.

Our genetics counselors are some of the best in the country, and are incredibly effective at diagnosing patients and matching them with effective treatments and clinical trials, says Steven Scherer, a professor of neurology and director of the Neurogenetics Therapy Center. Now we can utilize this expertise to design tomorrows therapies.

Read more at Penn Medicine News.

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Solving medical mysteries with genetics: The Penn Neurogenetics Therapy Center | Penn Today - Penn Today

SEATTLE, Sept. 12, 2022 (GLOBE NEWSWIRE) -- Data Bridge Market Research Published Latest Global Pharmacogenetics Testing in Psychiatry/Depression Market Study by in-depth analysis of the current scenario, the Market size, demand, growth pattern, trends, and forecast. This Pharmacogenetics Testing in Psychiatry/Depression market report studies the market and the healthcare industry comprehensively by considering several aspects. The report helps in achieving sustainable growth in the market, by providing well-versed, specific, and most relevant product and market information. Inputs from various industry experts, essential for the detailed market analysis, have been employed very carefully to generate this finest market research report. The company profiles of all the top market players and brands are listed in the Pharmacogenetics Testing in Psychiatry/Depression report which puts light on their moves like product launches, product enhancements, joint ventures, mergers and acquisitions and their effect on sales, import, export, revenue and CAGR values.

Data Bridge Market Research analyzes that the global pharmacogenetics testing in psychiatry/depression market is expected to reach the value of USD 2,133.49 million by 2029, at a CAGR of 9.5% during the forecast period. Anxiety accounts for the largest type segment in the market due to the increasing depression rate among the global population. This market report also covers pricing analysis, patent analysis, and technological advancements in depth.

Access PDF Sample Report (Including Graphs, Charts & Figures) @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-pharmacogenetic-testing-in-psychiatry-depression-market

Market Insights:-

Pharmacogenetic testing helps medical professionals by providing information on how a person metabolizes a medication. This information can help doctors and others avoid prescribing antidepressants that could produce undesirable outcomes. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in major depressive disorder (MDD). Pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The growing biotechnology sector, and increasing health expenditure, have accelerated the demand for pharmacogenetic testing in psychiatry/depression.

The growing prevalence of cancer disease, novel technology in the treatment of depression and/or other psychiatric conditions are increasing the adoption of pharmacogenetics testing in psychiatry/depression devices and procedures, and the rising preference for non-surgical procedures are the major drivers which propelled the demand for the market in the forecast period. However, the high cost associated with the tests, stringent regulation, and lack of awareness may expect to hamper the pharmacogenetics testing in psychiatry/depression market growth in the forecast period.

Some of the major players operating in the global pharmacogenetics testing in psychiatry/depression market are

Recent Developments

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Opportunity

Advances in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice for psychiatric disorders. Personalized medicine may be defined as a comprehensive, prospective approach to preventing, diagnosing, treating, and monitoring disease in ways that achieve optimal individual health care decisions. Over 100 medications now contain United States Food and Drug Administration (FDA) labelling related to potentially applicable pharmacogenomic biomarkers with technological advancements in healthcare. Also, new and advanced methods are being developed to promote pharmacogenetics testing in depression-like disorders. These tests use advanced genetic testing methods to give precise results to form a treatment regimen. The improvements in technology supporting tests improved accessibility of testing options, and the growing number of resources that help clinicians understand how to use this information when it is available are making this aspect of personalized or precision medicine a reality. Thus, providers need to become more aware of the scientific and clinical relevance of pharmacogenomic tests.

The tests also help to establish a meaningful relationship between a drug and the individual genetic makeup. This helps in deciding the drugs to be administered to the patient to treat major depressive disorders and other psychiatric conditions.

Market Dynamics:-

Drivers

Depression is a common illness worldwide, with an estimated 3.8% of the population affected, including 5.0% among adults and 5.7% among adults older than 60 years. Depression can become a serious health condition of mild to extreme severity, affecting the person to suffer greatly and can lead to suicide in the worst cases. Although over 45 antidepressants are available, suboptimal response poses a challenge and is considered a result of genetic variation, psychiatry/depression. Depending on the severity and pattern of depressive episodes over time, healthcare providers may offer psychological diagnosis such as behavioral activation, cognitive behavioral therapy, interpersonal psychotherapy, and/or antidepressant medication such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Different drugs are used for this kind of mental disorder.

With the growth in the prevalence of depression, the demand for pharmacogenetics testing is also increasing as it studies the effect of genetic variants intending to furnish tailored diagnosis. The market is expected to grow in foresting period.

Pharmacogenetics test aids the medical professional in choosing the best medicine for the person because the test searches for the gene variant that may be responsible for influencing the effect of the drug.

Medicine is becoming personal, and patients gradually express interest in improved outcomes and less adverse effects with personalized medications. Personalized medicine has the potential to tailor the therapy with a high safety margin and the best response. This trend is largely driven by genome sequencing improvements.

The move toward personal healthcare means changes in the manufacturing of medicines. Manufacturers are moving from creating small molecules to the combination of small molecule and gene therapies. Sponsors focus on replacing inefficient large-scale batch production with investment in new technology and producing personalized drugs.

Critical Insights Related to the Pharmacogenetics Testing in Psychiatry/DepressionIncluded in the Report:

Restraint

Most clinicians still lack confidence in pharmacogenetic (PGx) testing and subsequent data interpretation, indicating insufficient knowledge in this field. It emphasizes the need to improve literacy among healthcare professionals regarding expertise in and understanding of pharmacogenetic (PGx) testing.

Lack of practitioners awareness about the possibilities of pharmacogenetics and poor or insufficient explanation of the test results also reduce personalization technologies for patients. In addition to developing thematic training courses at medical universities, including the educational cycles in continuing professional education systems, and free placement of information for practicing doctors are required: academic internet portals, webinars, etc. A clinical pharmacologist plays a crucial role in the implementation of pharmacogenetic testing.

The competence of a clinical pharmacologist in the field of pharmacogenetics is critical: he or she is the one who organizes the application of genotyping in clinical practice, interprets tests, and informs doctors about the possibilities of pharmacogenetics for patients with specific nosologies, that is, acts as the main link between the scientific world, the healthcare system and practicing physicians in the process of introducing pharmacogenetics.

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Challenge

The concerns regarding the efficacy and safety of products have caused most governments to develop regulatory agencies and policies to look after the development of new medical products or tests. The use of these medical products can be done after passing stringent regulatory standards, which ensure the product is safe, well studied, and has no adverse reactions.

The recent guidelines and the amendment have adequate guidance for manufacturers. International regulations such as food, drug, and administration play a major role in the new launch of medical products or tests into the market. Thus, it can be a major restraint for the market. Therefore, strict government regulation on new products and instrument approval will likely impact the market.

Segmentation: Pharmacogenetics Testing in Psychiatry/Depression Market

Global pharmacogenetics testing in psychiatry/depression market is segmented into type, test type, gene type, patient type, product, end user, and distribution channel. The growth among segments helps you analyze niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

By Type

By Test Type

By Gene Type

By Patient Type

By Product

By End User

By Distribution Channel

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Global Pharmacogenetics Testing in Psychiatry/Depression Market Regional Analysis/Insights

The pharmacogenetics testing in psychiatry/depression market is analyzed, and market size information is provided by the type, test type, gene type, patient type, product, end user, and distribution channel.

The countries covered in pharmacogenetics testing in psychiatry/depression market report are U.S., Canada, Mexico, Germany, France, U.K., Italy, Spain, Russia, Turkey, Netherlands, Switzerland, Hungary, Austria, Lithuania, Ireland, Norway, Poland, and the rest of Europe, China, Japan, India, South Korea, Singapore, Thailand, Malaysia, Australia, Vietnam, Philippines, Indonesia and rest of Asia-Pacific, UAE, Israel, South Africa, Egypt, Kuwait and rest of the Middle East and Africa, Brazil, Argentina, Peru and, rest of South America.

In 2022, North America is dominating due to the presence of key market players in the largest consumer market with high GDP. The U.S is expected to grow due to the rise in technological advancement in pharmacogenetics testing.

North America is dominating the market. The increasing investment in R&D and increasing adoption of pharmacogenetics testing as an option for formulating treatment regimens is expected to boost the market growth. The U.S. dominates the North American region due to the strong presence of advanced technology providers such as Eurofins Scientific, Illumina, Inc., and others. The U.K. dominates Europe due to the increasing demand from emerging markets and the expansion of pharmaceutical industries. China dominates the Asia-Pacific region due to increased healthcare expenditure.

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Pharmacogenetics Testing in Psychiatry/Depression Market Will Rise at a CAGR 9.5% by 2029 and is segmented by Test Type, Gene Type, Patient Type,...

image:The research is led by professor UrFU Dmitri Alexandrov. view more

Credit: UrFU

Physicists and mathematicians from the Ural Federal University (UrFU) have created a complex mathematical model that calculates the distribution of nanoparticles (in particular, viruses) in living cells. The mathematical model helps finding how the nanoparticles cluster (merge into a single particle) inside cells, namely in cellular endosomes, which are responsible for sorting and transporting proteins and lipids. These calculations will be useful for medical purposes because, on the one hand, they show the behaviour of viruses when they enter cells and seek to replicate. And on the other hand, the model allows to accurately calculate the amount of medication needed for therapy, so that the treatment is as effective as possible and with minimal side effects. The model description and the results of calculations, the scientists publishedin the journal Crystals.

The processes in cells are extremely complex, but in simple words, the viruses use different variants to reproduce. Some of them deliver the genetic material directly to the cytoplasm. Others use the endocytosis pathway: they deliver the viral genome by releasing it from the endosomes. If viruses linger in the endosomes, the acidity increases and they die in the lysosomes, says Dmitri Alexandrov, Head of the Laboratory of Multiscale Mathematical Modeling at UrFU. So, our model has allowed to find out, first, when and which viruses "escape" from endosomes in order to survive. For example, some influenza viruses are low pH-dependent viruses; they fuse with the endosome membrane and release their genome into the cytoplasm. Secondly, we found that it is easier for viruses to survive in endosomes during clustering, when two particles merge and tend to form a single particle.

As the scientists explain, the mathematical model will also be useful in tumor targeting therapy: many cancer therapies depend on when and how nanoparticles of a drug saturate cancer cells. And the model will help to calculate this parameter.

In addition, understanding the behavior of viruses in cells is important for the development of vaccines and drugs, as well as for gene therapy, which treats diseases that conventional medicine cannot cope with. For example, various adenovirus-based vectors and lipid particles are used as a platform for gene delivery to treat the disease. But their limited ability to "slip out" of the endosomes also limits their use as deliverers.

Nanoparticles smaller than 100 nanometers are becoming increasingly important tools in the modern medicine. Its applications range from nanodiagnostics to radiation therapy for cancer. For example, pH-sensitive nanoparticles mimicking viruses are used for targeted delivery of antitumor drugs. This is how drugs are delivered from whole organs to individual cells, says Head of the Laboratory of Stochastic Transport of Nanoparticles in Living Systems (UrFU) Eugenya Makoveeva.

Reference

Endosome is a membrane intracellular organelle. It is responsible for sorting and transporting proteins and lipids; occur during the fusion and development of endocytic vesicles. In the process of maturation, the endosome goes through several stages, as a result of which it turns into a lysosome. Mature endosomes reach sizes of 300-400 nanometers.

Analysis of Smoluchowskis Coagulation Equation with Injection

17-Aug-2022

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Scientists have created a mathematical model for the dynamics of nanoparticles and viruses in cells - EurekAlert

MENLO PARK, Calif. & DALLAS--(BUSINESS WIRE)--ReCode Therapeutics, a genetic medicines company using superior delivery to power the next wave of mRNA and gene correction therapeutics, announced today that Fierce Biotech has named it as one of 2022s Fierce 15 biotechnology companies, designating it as one of the most promising early-stage biotechnology companies in the industry.

In recent years, weve seen major advances in mRNA and gene correction therapeutics. However, their utility has been limited by current delivery systems. Thanks to the pioneering science behind ReCodes novel selective organ targeting (SORT) lipid nanoparticle (LNP) technology, we are poised to transform the paradigm for genetic medicines with the ability to precisely target and deliver any form or combination of genetic cargo to specific organs and cells, beyond the liver, said Shehnaaz Suliman, M.D., MBA, M.Phil., chief executive officer and board member, ReCode Therapeutics. It is an honor to be recognized among this distinguished group of Fierce 15 industry innovators.

ReCode is differentiated by its first-in-class modular genetic medicines delivery platform. The companys selective organ targeting (SORT) lipid nanoparticle technology (LNP) platform is the foundation for its pipeline. Pioneered by co-founder Professor Daniel J. Siegwart, Ph.D., of the University of Texas, and described by Nature as one of the Seven Technologies to Watch in 2022, ReCodes SORT LNP platform is an innovation beyond the lipid delivery system used by the mRNA COVID vaccines and novel RNA and gene correction therapeutics.

LNPs are used to package and deliver genetic cargo such as mRNA. When delivered into the blood, first-generation LNPs are primarily taken up by the liver, which limits their utility for broad therapeutic applications. ReCodes SORT LNPs are engineered with a biochemically distinct fifth lipid to help the body sort and direct the LNPs to other targeted organs such as the lung and spleen, with the ability to bypass the liver, if desired.

Beyond its highly selective targeting capability, ReCodes SORT LNP platform is further distinguished by its versatility in both mode of administration (including IV, inhaled, subcutaneous, intramuscular and intrathecal), and the diversity of genetic cargo that can be delivered (including mRNA, siRNA, DNA, gene correction components and mixed cargoes). Together, these qualities offer vast opportunities to address a wide range of unmet medical needs through a precision medicine approach that delivers the right medicine to the right organs and cells using the optimal mode of administration.

In June, ReCode announced the close of a Series B extension financing round which infused a total investment of $200M to fund the diversification of ReCodes pipeline into central nervous system, liver, and oncology indications, while continuing to advance ReCodes lead mRNA programs for primary ciliary dyskinesia and cystic fibrosis into the clinic.

The Fierce 15 celebrates the spirit of being fierce championing innovation and creativity, even in the face of intense competition. This is Fierce Biotechs 20th annual Fierce 15 selection. An internationally recognized daily report reaching a network of over 450,000 biotech and pharma industry professionals, Fierce Biotech provides subscribers with an authoritative analysis of the day's top stories. Every year Fierce Biotech evaluates hundreds of early-stage companies from around the world for its annual Fierce 15 list, which is based on a variety of factors such as the strength of its technology, partnerships, venture backers and a competitive market position.

About Fierce Biotech

Fierce Biotech is the biotech industry's daily monitor, an email newsletter and web resource providing the latest biotech news, articles, and resources related to clinical trials, drug discovery, FDA approval, FDA regulation, patent news, pharma news, biotech company news and more. More than 450,000 top biotech professionals rely on Fierce Biotech for an insider briefing on the day's top stories. Signup is free at http://www.fiercebiotech.com/signup.

About ReCode Therapeutics

ReCode Therapeutics is a genetic medicines company using superior delivery to power the next wave of mRNA and gene correction therapeutics. ReCodes selective organ targeting (SORT) lipid nanoparticle (LNP) platform is a next-generation, genetic medicines technology that enables precise delivery to target organs and cells beyond the liver. The SORT LNP platform is the foundation for ReCodes pipeline of disease-modifying mRNA and gene correction therapeutics. ReCodes lead programs are focused on primary ciliary dyskinesia and cystic fibrosis. ReCode is leveraging its SORT LNP platform and nucleic acid technologies to expand its pipeline with therapeutics that use mRNA-mediated replacement and gene correction in target organs with precision targeting of disease-relevant cells. For more information, visit http://www.recodetx.com and follow us on Twitter @ReCodeTx and on LinkedIn.

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Fierce Biotech Names ReCode Therapeutics as One of its Fierce 15 Biotech Companies of 2022 - Business Wire

NEW YORK Roche's Foundation Medicine announced on Monday that it will collaborate with Relay Therapeutics to develop FoundationOne CDx as a companion diagnostic for Relay's RLY-4008, an investigational FGFR2 inhibitor.

The drug is currently being evaluated for use in patients with FGFR2-mutated cholangiocarcinoma, or bile duct cancer, and other solid tumors, the companies said in a statement. If the therapy and FoundationOne CDx as a companion diagnostic are approved, the test would be used to identify patients with FGFR2 fusions and select rearrangements in cholangiocarcinoma who may be appropriate for treatment with the drug.

FGFR2 is a receptor tyrosine kinase that is often altered in certain cancers, and RLY-4008 is currently being evaluated in a clinical trial in patients with advanced or metastatic FGFR2-altered solid tumors, the companies said.

"FGFR2-mutated cholangiocarcinoma is an aggressive condition that's generally diagnosed in advanced stages when prognosis is poor and treatment options are limited," Don Bergstrom, president of R&D at Relay Therapeutics, said in a statement. "We're proud to partner with the leader in companion diagnostic approvals as we work to advance this potentially life-changing therapy and create access to it once approved."

Next-generation sequencing-based FoundationOne CDx is used as a companion diagnostic for a variety of drugs and detects substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, along with genomic signatures such as microsatellite instability and tumor mutational burden using DNA isolated from formalin-fixed, paraffin-embedded tumor tissue specimens.

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Foundation Medicine, Relay Therapeutics to Develop FoundationOne CDx for FGFR2 Inhibitor - GenomeWeb

Drug development and manufacturing have undergone a seismic shift in the last two decades,1from blockbuster small molecules to highly personalized biologics2and cell and gene therapies. Because these therapies are designed for specific populations, they dont require the kinds of large-scale manufacturing operations that many companies and contract development and manufacturing organizations (CDMOs) have optimized.

While the drugs may offer significant value for patients, smaller batch medicines may not be financially feasible for a larger company to manufacture especially if they have a broader pipeline. Companies are now working to address this disconnect, optimizing their processes for smaller batch biologics.

This article discusses one of the key areas where innovation is needed: downstream processing. Surveys show downstream processing remains a serious bottleneck one that significantly impacts overall production.3Surging demand for treatments and vaccines fueled by the COVID-19 pandemic has only exacerbated these bottlenecks.4,5Many have been exploring alternative processes and products, such as new chromatography columns that better reflect modern manufacturing needs. Biopharmaceutical leaders urgently need these kinds of solutions to improve the productivity, efficiency and flexibility of downstream processing.

As the name suggests, precision medicine is about targeting medical care to each person to improve outcomes and reduce side effects. This field has advanced rapidly over the last two decades, with highly selective biologics and new modalities including bispecifics, trispecifics, antibody-drug conjugates (ADCs), cytokines, and bespoke cell and gene therapies (CGT). Each of these modalities introduces new manufacturing challenges, many related to the potency of the drugs.

ADCs are a validated modality and one that oncology players are increasingly recognizing as important to their discovery and development efforts. We are truly in an ADC renaissance with 11 approved ADCs and more than 100 in development, said Engin Ayturk, PhD, senior director for process engineering and bioconjugation for Mersana Therapeutics. Mersana Therapeutics is advancing a pipeline of novel ADCs, including its lead candidate UpRi (upifitamab rilsodotin), which is being studied in ovarian cancer.

Medicines with greater potency generate increasingly complex regulatory requirements. As a result, the processing of these high-potency molecules including ADCs requires specialized equipment and expertise. Developers must find manufacturing partners that can safely handle high-potency molecules while meeting regulatory requirements.

Technologies such as next-generation sequencing (NGS) provide key insights into the drivers of disease,6,7and how individuals respond to medications. Over the last two decades, this information has helped usher in a new era in precision medicine, targeting unique mutations in cancer or specific pathways in rare or autoimmune diseases (Figure 1). Since these are medications that treat diseases in a target population, these orphan drugs tend to be produced in small batches.

Figure 1: Count of FDA orphan drug/precision medicine designations and approvals by year (1983-2019).8

The rise in disposable single-use technologies has also impacted downstream manufacturing processes and efficiencies. Single-use reactors, membranes and chromatography systems cut down on laborious cleaning processes, giving companies and CDMOs greater flexibility to handle a variety of projects. For smaller-scale manufacturing, they can more readily change out the single-use products and switch to a new therapy. This changeover capability reduces cross-contamination,9provides better bioburden control and ensures companies manufacture high-purity products. Overall, single-use technologies decrease the time and resources spent on clean-up and set-up between different drugs, improving operational efficiency.

You can no longer build a facility that handles just one drug. Your facility must be able to handle more than one drug efficiently, and more and more, were seeing single-use technologies enable that, explained Kasper Mller, PhD, chief technology officer of AGC Biologics. AGC Biologics is a global CDMO offering microbial and mammalian capabilities as well as CGT, fulfilling early-phase through late-phase projects at both small and large scales.

Mller further stated, Disposable single-use technology is rapidly fueling the innovations we see in manufacturing today. As an example, in upstream processing, we developed and implemented the 6-PackTM scale-out concept, which allows us to inoculate and harvest several main bioreactors from one seed train to establish flexible process scaling.

He says this capability is important because manufacturing volume after launch is uncertain for some molecules, even if clinical trial and launch manufacturing is built at a standard 2000L scale. The 6-PackTM scale-out technology allows manufacturers to adjust scale very quickly after launch.

The biopharma experts we interviewed agreed that disposables are now used in every step of the manufacturing process, from buffer preparation, buffer storage and eluate collection all the way to the medication dispensing and weighing rooms. However, some technologies, such as single-use chromatography columns and membranes, have yet to see widespread adoption despite eliminating time consuming packing of columns, qualification, storage and re-validation of oversized columns, and increased throughput. These are expected to become more common in the near future.

A while ago, it became clear that membranes are a great alternative to columns and were becoming more widely used. Weve especially seen great success with flowthrough membranes, Mller explained. Overall, I think were approaching a future in manufacturing where we implement fully disposable processes including all the chromatography steps that support the flexibility that is needed in rare disease and small volume manufacturing.

While not unique to the biopharma industry, the gradual shift from traditional batch processing to continuous processing has also impacted therapeutic manufacturing. Instead of starting and stopping each batch, continuous processing operates as a non-stop cycle. This approach can reduce the cost of manufacturing precision medicines without requiring an increase in scale.10,11

In continuous bioprocessing, continuous chromatography processes are crucial for achieving high purity products. A continuous chromatography process uses several chromatography columns in a concurrent manner: as loading is carried out in the first column, all the other steps washing, elution, regeneration and re-equilibration are carried out in the other columns.12A study that performed a cost analysis of traditional batch processing versus continuous processing for 200 kg of monoclonal antibody (mAb) production found that the latter reduced downstream processing cost of goods by approximately $9/kg.13,14

For smaller biopharmaceutical companies working to produce high-value precision medicines, the new wave of approvals is both exciting and overwhelming. One of those challenges is finding the right facility to handle the manufacturing of each medication.

Facility fit is a big challenge and forward thinking is essential, said Ayturk. Most manufacturing partners are optimized for standard or generic processes that are significantly larger in capacity. There are gaps in finding partners that offer variety in scales of operation and, provide services for drugs that require high-potent handling and/or integrated processes, analytical development and release activities. Finding a manufacturing partner that can handle IND-enabling activities and production needs against aggressive timelines can be challenging.

The COVID-19 pandemic has put pressure on supply chains15and staffing, with many CDMOs and CMOs solidly booked for a year or more. Smaller biotech and biopharma companies without manufacturing abilities that depend on CDMOs can end up deprioritized or paying a premium as they compete for manufacturing capacity alongside larger-scale drugs.

As one engineer at an emerging cancer immunotherapy company puts it: If you have a GMP run that needs to be completed in seven months, but the lead time on the resins and products you need is two years, that is a challenge.

The new wave in precision medicine manufacturing coupled with the COVID-19 pandemic is driving a shortage in new resins and buffers needed for downstream processing. Some market players are quoting lead times of several months to over a year.

To help mitigate these risks, many groups are proactively identifying a second supplier for crucial goods. For example, manufacturers that require a specific resin for removal of a known impurity should find backup products that have a similar resin or membrane. This extra layer of security can help companies meet the deadlines required for clinical trials or for patients who need those therapies the most.

Other backup plans can prove more laborious. In some cases, when weve realized that our columns dedicated to at-scale GMP clinical resupply batches were not going to be delivered on time, weve had to revisit conventional ways of doing work and rebuilt the bridges between single-use and re-use manufacturing approaches, said Ayturk. Weve re-established cycling and resin life-time studies and re-introduced cleaning and storage regimens into our processes to ensure uninterrupted supply to clinic because patients waiting.

The goal for both biopharma companies and CDMOs is to be efficient with drug production in order to ensure their medications reach the populations that need them the most. However, as noted above, this goal can be disrupted by supply chain shortages and a lack of available manufacturing capacity.

Drug developers beginning their manufacturing journey or looking to adapt can learn from these disruptions and plan accordingly. One important step in this direction is evaluating alternative technologies for cleaning up impurities.

Historically, the biopharmaceutical industry has been slow to adopt new technologies for good reason. Regulatory agencies and other stakeholders value proven products and consistency. However, at a certain point, the latest technology must become the status quo to keep up with the evolution in drug modalities and manufacturing processes.

CDMOs sometimes struggle to convince clients that these new technologies will work for their products. Naturally, nobody wants to be the first when it comes to implementing new technology. They want to know how many approved INDs have used that technology, explained Mller. However, we have also seen more development and a strong push for implementing new technology and innovation by the FDA over the last ten years. And so clients do expect that new technologies may be incorporated into their workflows. We routinely make agreements with clients to implement specific technology that solves a unique problem for their product.

There are now both technical and supply chain motivations for adopting new chromatography technologies. As one bioprocessing engineer shared, This is what intrigued us about GOREs membrane technologythe need to have backup or replacement resins that offer speed, efficiency, and long-term cost savings. Ultimately, it is about being able to get the medicines onto the market in order to save lives. GORE had excellent lead times.

GORE Protein Capture Devices with Immobilized Protein A are intended for the affinity purification of precision medicines containing an Fc region in process development to initial GMP clinical applications. The Protein Capture Devices leverage a unique expanded polytetrafluoroethylene (ePTFE) membrane solution that helps to bridge the gap that has long existed between innovations in upstream and downstream processing.

Pre-packed GORE Protein Capture Devices significantly boost productivity with high binding capacity and fast flow rate, enabling a faster path to clinical trials.

As biopharma manufacturers continue to seek alternate solutions in streamlining downstream processes and embrace those with the most viability and efficiency, bottlenecks will be reduced, and productivity will increase. This will have a positive impact as manufacturers shift their focus to precision medicine innovations where ultimately, patients will have access to wider range of therapeutics for a various disease conditions.

References

1. Congressional Budget Office. Research and development in the pharmaceutical industry. Published August 4, 2021. Accessed March 25, 2022. https://www.cbo.gov/publication/57126.

2. Yamamoto Y, Kanayama N, Nakayama Y, Matsushima N. Current status, issues and future prospects of personalized medicine for each disease.J Pers Med. 2022;12(3):444. doi: 10.3390/jpm12030444

3. Bioplan Associates. 13th annual report and survey of biopharmaceutical manufacturing capacity and production. 2016. http://bioplanassociates.com/wp-content/uploads/2016/07/13th-Annual-Biomfg-Report_BioPlan-TABLE-OF-CONTENTS.pdf

4. Challener C. Maximum output starts with optimized upstream processing. BioPharm International. 2021;34(4):10-17. Published April 2, 2021. Accessed August 23, 2022. https://www.biopharminternational.com/view/maximum-output-starts-with-optimized-upstream-processing

5. Barone P, Keumurian F, Wiebe M, et al. The impact of SARS-CoV-2 on biomanufacturing operations. BioPharm International. 2020;33(8):34-38. Accessed February 7, 2022. https://www.biopharminternational.com/view/the-impact-of-sars-cov-2-on-biomanufacturing-operations

6. Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol Mech Dis. 2019;14(1):319-338. doi: 10.1146/annurev-pathmechdis-012418-012751

7. Adams DR, Eng CM. Next-generation sequencing to diagnose suspected genetic disorders. N Engl J Med. 2018;379(14):1353-1362. doi: 10.1056/NEJMra1711801

8. Miller KL, Fermaglich LJ, Maynard J. Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases. Orphanet J Rare Dis. 2021;16(1):265. doi: 10.1186/s13023-021-01901-6

9. Sandle T, Saghee MR. Some considerations for the implementation of disposable technology and single-use systems in biopharmaceuticals. J Commer Biotechnol. 2011;17(4):319-329. doi: 10.1057/jcb.2011.21

10. Macdonald GJ. Disrupting downstream bottlenecks. GEN - Genetic Engineering and Biotechnology News. Published June 14, 2018. Accessed February 4, 2022. https://www.genengnews.com/magazine/320/disrupting-downstream-bottlenecks/

11. Tripathi NK, Shrivastava A. Recent developments in bioprocessing of recombinant proteins: expression hosts and process development. Front Bioeng Biotechnol. 2019;7:420. doi: 10.3389/fbioe.2019.00420

12. De Luca C, Felletti S, Lievore G, et al. Modern trends in downstream processing of biotherapeutics through continuous chromatography: The potential of Multicolumn Countercurrent Solvent Gradient Purification. Trends Analyt Chem. 2020;132:116051. doi: 10.1016/j.trac.2020.116051

13. Klutz S, Holtmann L, Lobedann M, Schembecker G. Cost evaluation of antibody production processes in different operation modes. Chem Eng Sci. 2016;141:63-74. doi: 10.1016/j.ces.2015.10.029

14. Somasundaram B, Pleitt K, Shave E, Baker K, Lua LHL. Progression of continuous downstream processing of monoclonal antibodies: Current trends and challenges. Biotechnol Bioeng. 2018;115(12):2893-2907. doi: 10.1002/bit.26812

15. Singh A, et al. Decision-Making Models for Healthcare Supply Chain Disruptions: Review and Insights for Post-Pandemic Era. JGBC. 2022. Singh A, Parida R. Decision-making models for healthcare supply chain disruptions: review and insights for post-pandemic era. JGBC. 2022. doi: 10.1007/s42943-021-00045-5

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Downstream Processing in the Age of Precision Medicine: Trends and Challenges - Technology Networks

(Boston)Boston University CityLab, a biotechnology learning laboratory for middle and high school teachers and their students, has received a five-year, $1.3 million Science Education Partnership Award (SEPA) grant from the National Institute of General Medical Sciences of the National Institutes of Health (NIH). This grant will allow CityLab to develop, implement and evaluate a new curriculum for high school students that explores genome editing and builds awareness about the importance of diversity, equity, inclusion and social justice in STEM and the biomedical sciences. The grant to Boston University CityLab is the only new SEPA award made to a Massachusetts institution in 2022.

CityLab, a partnership between Boston Universitys School of Medicine and Wheelock College of Education & Human Development, was first funded by the NIH SEPA program in 1991 at the inception of the program and is one of just a few programs that have been continuously operating since that time. The new grant project, "Mystery of the Crooked Cell 2.0: CityLabs Next Generation Socioscientific Approach to Gene Editing," addresses the imperative that NIH's pre-college activities focus on biomedical workforce preparedness, especially for underrepresented minorities (URM).

This project will expand CityLabs Mystery of the Crooked Cell hands-on, inquiry-based curriculum supplement that focuses on the molecular basis of sickle cell disease by incorporating state-of-the-art gene editing content that is immersed with socioscientific reasoning (SSR). This project will reach close to 600 local URM students and, through planned web-based dissemination of the finished curriculum, will reach thousands of students, explained principal investigator Carl Franzblau, PhD, professor of biochemistry at Boston University School of Medicine and the founder of CityLab.

According to principal investigator Donald DeRosa, EdD, clinical associate professor and science education program director at Boston University Wheelock College of Education & Human Development, an SSR approach places science content in a meaningful social context and motivates students to take ownership of their learning. SSR skills include realizing the complexity of the content and context of an issue, analyzing an issue from multiple perspectives, seeking out sources of bias in data and considering how and whether scientific investigations can advance understanding of an issue.

Genome editing is becoming part of the physicians toolkit, so teaching young people about this important and rapidly advancing field will prepare them to be informed patients and, we hope, will position them to enter careers in the biomedical sciences or health professions, highlighted principal investigator Carla Romney, ScD, director of research for CityLab.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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BU receives NIH award to increase diversity of STEM and biomedical science workforce - EurekAlert

There is no one-size-fits-all algorithm for AI that enables drug developers to apply it and quickly identify whatever features they seek. Finding an answer to this dilemma has great implications for the field of precision medicine.

Currently, researchers are selecting best-of-breed algorithms in a modular approach to build customized analytics engines that answer specific questions in a way that is both unbiased and reproducible.

We still dont have a gold standard in terms of implementing and applying reproducible AI/ML approaches, said Zeeshan Ahmed, Ph.D., assistant professor of medicine at Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, in an interview with BioSpace.

As yet, there has been very little effort to organize and understand the many computing approaches in this field.

Key AI/ML Objectives for Precision Medicine

A review published in Briefings in Bioinformatics is among the first. Ahmed and colleagues examined five years of literature in whole-genome or whole exome sequencing to identify 32 of the most frequently used AI/ML algorithms and approaches used to deliver precision medicine insights.

The team compared scientific objectives, methodologies, data sources, ethics and gaps for each of those approaches.

For AI/ML to be more useful for drug developers, several things are required. Chief among them, Ahmed said, are:

During cases, when data is of high volume, it is important to ensure the right balance between training and actual datasets to avoid overfitting, Ahmed noted.

For AI/ML to be most useful, the data should be standardized to enable more accurate searches. Ensuring the data uses the same terms to refer to the same elements helps ensure that all the relevant information can be identified and analyzed.

There should be a method to correct errors in the data, too. Data that is entered by hand, for instance, may well have inaccuracies. The study data also should span multiple diseases and distinct populations to reflect the broad way in which diseases, conditions and symptoms present.

The Role of AI/ML in COVID-19 Drug Repurposing

Recent research in Biomedicine & Pharmacotherapy, conducted by Kyung Hyun Choi from the Jeju National University in Korea and colleagues noted the value of ML and deep learning in drug repurposing for COVID-19 therapeutics. Those methods helped them distinguish between drug targets and gene products that affect target activity.

Each type of analysis had its own group of algorithms, Choi explained in the paper. Types of analyses used for machine learning included k-nearest neighbors (a non-supervised learning method), random forest and support vector machine, among others.

Deep learning techniques included artificial neural networks, convolutional neural networks and long short-term memory. AI algorithms were used for link prediction, node prediction or graph prediction and other tasks.

In applying AI/ML to research, Choi and colleagues wrote, The limitationsinclude the inconsistencyin biological networks, as well as challenges associated with various networks that can lead to bias in the outcome. To overcome those issues, he recommended using heterogeneous data from multiple sources to enhance the reliability of analyses.

Another study published in Current Drug Targets last year reviews ML tools used to identify biologically active compounds from among millions of candidates.

It found, among other things, that the support vector machine (SVM) algorithm was more effective than others in indicating the classification model best used for human intestinal absorption predictions. However, the quantitative structure-activity relationship (QSAR) model predicted flavonoid inhibitory effects in specific indications. Clearly, the choice of algorithm matters.

Decoding the Black Box

Until a few years ago, AI often was considered a black box that ingested data and expelled findings without providing researchers with the details needed to understand how those results were derived.

Youre learning how thousands of inputs connect to hundreds or thousands of outputs, David Longo, co-founder and CEO of Ordaos, told BioSpace. Machine learning algorithms learn the intrinsic relationships between for example amino acids and motifs and domainsin a nonlinear, complex way, so theres still a kind of black box element to AL/ML, depending on how you construct it.

Generally, modern AI/ML algorithms allow some degree of insight into how individual algorithms reach their conclusions.

For example, Ordaos, which develops mini-proteins, provides a trace-back of every single amino acid that was changed and how that affected the properties that come out of that protein, Longo said. For researchers, thats a huge benefit.

Innovation in the field of AI/ML today is not necessarily around creating new individual components, but putting them together in interesting ways, Longo continued.

He cited Ordaos multitask learning model as an example.

Traditionally, ML models were developed by training the algorithm in a specific area a structure predictor would just train on structures and, with a few more steps, create a model. Using that model for another, slightly different purpose, required retraining. Ordaos model, in contrast, learns from multiple tasks simultaneously, somewhat countering Ahmeds view of algorithm specificity.

Selecting the Right Algorithms

AI/ML analytic approaches have the potential to help develop enhanced, systems-level understanding of disease mechanisms and treatment impacts, and can replace the homogeneity of existing genetic and statistical approaches with heterogeneity. Realizing that value, however, requires selecting the right algorithms for the job.

It is important to measure and avoid algorithmic bias, Ahmed said. Classifying tasks based on available predictor variables is a key step to correctly address the problem of choosing a suitable AI/ML algorithm.

In my lab, Ahmed said, We practice AI/ML-driven personalized medicine. We are generating AI/ML-ready datasets based on clinical and multi-omics/genomics profiles and are developing automated pipelines to analyze and perform predictive analysis.

Furthermore, we are addressing ethical issues, which involve protecting health information associated with multi-omics/genomic datasets, he continued.

The analytics trend is shifting from generating big data to analyzing and interpreting that data and using it predictively. For those predictions to be accurate, the underlying assumptions also must be accurate, and that requires selecting the right algorithms for the questions.

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Leveraging Best-of-Breed Algorithms for Accuracy in Precision Medicine - BioSpace

Getting from point A to point B has never been easier thanks to digital maps on our smartphones. With the swipe of a finger, we can plan a route to the grocery store, scope out a hiking trail or pick a perfect vacation destination. Soon, biomedical researchers will have a similar tool to easily navigate the vast network of cells in the human body.

The Human BioMolecular Atlas Program, or HuBMAP, is an international consortium of researchers with a shared goal of developing a global atlas of healthy cells in the human body. Once completed, the resource will be made freely available to drug developers and clinical researchers who could use it to shape the development of specialized medical treatments.

The idea behind HuBMAP is akin to the National Institutes of Healths Human Genome Project, which sequenced every single gene in the human body. Completed almost 20 years ago, the massive undertaking kickstarted a renaissance in clinical research and laid the groundwork for innovative approaches to gene-based therapies. But instead of collecting genetic information on the whole organism level, HuBMAP goes deeper with the goal of mapping gene expression, proteins, metabolites and other information in different types of cells across various organs and tissues.

The next step of turning this vast wealth of data into a user-friendly tool is managed by bioinformaticians at the University of Pittsburgh, the Pittsburgh Supercomputing Center (PSC), Carnegie Mellon University and Stanford University. The teams recently received $20 million in renewed funding from the NIH to continue these efforts.

Creating an ecosystem that can connect all the different pieces of data into a single large knowledge resource is a tough job, but thats what this team has special expertise in. We are good at integrating all kinds of various pieces of software and making them run, said co-lead of the Pittsburgh HuBMAP Infrastructure and Engagement Component Jonathan Silverstein, a professor in theDepartment of Biomedical Informaticsat Pitt.

The team, led by Silverstein, who is also a chief research informatics officer at Pitt and UPMCsInstitute for Precision Medicine, and PSCs Scientific Director Phil Blood, will embark on a long journey of annotating vast amounts of molecular-level data from thousands of tissue samples collected in over 60 institutions across the country. A locally maintained and developed hybrid cloud infrastructure for data integration and software development is being used to mold the resulting library of genetic and protein signatures of healthy cells into a comprehensive map.

The HuBMAP Computational Tools Component, led by Matthew Ruffalo of Carnegie Mellons Computational Biology Department, has developed computational pipelines for processing these molecular datasets, allowing for efficient data integration across data types, tissues and more.

The team is also involved in projects aimed at creating an atlas of aging and senescent cells (SenNet) and building a framework for studying molecular markers of breast cancer.

In addition to research, the HuBMAP and SenNet consortia are really helping to shape the ecosystem and the culture around projects that this work will impact, said Kay Metis, SenNet program manager at Pitt. This project has the potential to impact Alzheimers and aging research and make a big difference to the direction of medical research going forward. I love being part of the effort to contribute to the social impact of what a project of this scale can accomplish.

The expertise in molecular biology and clinical data, combined with experience in managing research consortiums and deep knowledge of software integration, along with computing resources provided by the PSC, makes Pittsburgh uniquely capable of handling a complex task such as HuBMAP.

I came to Pitt because it is a place with great depth of interest and scientific expertise and people here are open to building collaborations, not only across Pittsburgh but worldwide. We have created a team that is unbounded not only on the clinical and biological data side, but also on the technology side, Silverstein said.

Ana Gorelova, image by Getty

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Pitt researchers are leading the way toward a Google Maps of cells - University of Pittsburgh

Nanotechnology, nicknamed "the manufacturing technology of the twenty-first century," allows us to manufacture a vast range of sophisticated molecular devices by manipulating matter on an atomic and molecular scale. These nanomaterials possess the ideal properties of strength, ductility, reactivity, conductance, and capacity at the atomic, molecular, and supramolecular levels to create useable devices and systems in a length range of 1-100 nm. The materials' physical, chemical, and mechanical characteristics differ fundamentally and profoundly at the nanoscale from those of individual atoms, molecules, or bulk material, which enables the most efficient atom alignment in a very tiny space. Nanotechnology allows us to build various intricate nanostructured materials by manipulating matter at the atomic and molecular scale in terms of strength, ductility, reactivity, conductance, and capacity [1,2].

"Nanomedicine" is the science and technology used to diagnose, treat, and prevent diseases. It is also used for pain management and to safeguard and improve people's health through nanosized molecules, biotechnology, genetic engineering, complex mechanical systems, and nanorobots [3]. Nanoscale devices are a thousand times more microscopic than human cells, being comparable to biomolecules like enzymes and their respective receptors in size. Because of this property, nanosized devices can interact with receptors on the cell walls, as well as within the cells. By obtaining entry into different parts of the body, they can help pick up the disease, as well as allow delivery oftreatment to areas of the body that one can never imagine being accessible. Human physiology comprises multiple biological nano-machines. Biological processes that can lead to cancer also occur at the nanoscale. Nanotechnology offers scientists the opportunity to experiment on macromolecules in real time and at the earliest stage of disease, even when very few cells are affected. This helps in the early and accurate detection of cancer.

In a nutshell, the utility of the nanoscale materials for cancer is due to the qualities such as the ability to be functionalized and tailored to human biological systems (compatibility), the ability to offer therapy or act as a therapeutic agent, the ability to act as a diagnostic tool, the capability to penetrate various physiological barriers such as the blood-brain barrier, the capability to accumulate passively in the tumor, and the ability to aggressively target malignant cells.

Nanotechnology in cancer management has yielded various promising outcomes, including drug administration, gene therapy, monitoring and diagnostics, medication carriage, biomarker tracing, medicines, and histopathological imaging. Quantum dots (QDs) and gold nanoparticles are employed at the molecular level to diagnose cancer. Molecular diagnostic techniques based on these nanoparticles, such as biomarker discovery, can properly and quickly diagnose tumors. Nanotechnology therapeutics, such as nanoscale drug delivery, will ensure that malignant tissues are specifically targeted while reducing complications. Because of their biological nature, nanomaterials can cross cell walls with ease. Because of their active and passive targeting, nanomaterials have been used in cancer treatment for many years. This research looks at its applications in cancer diagnosis and therapy, emphasizing the technology's benefits and limitations [3-5]. The various uses of nanotechnology have been enumerated in the Table 1.

Early cancer detection is half the problem solved in the battle against cancer. X-ray, ultrasonography, CT, magnetic resonance imaging (MRI), and PET scan are the imaging techniques routinely used to diagnose cancer. Morphological changes in tissues or cells (histopathology or cytology) help in the final confirmation of cancer. These techniques detect cancer only after visible changes in tissues, by which time the cancer might have proliferated and caused metastasis. Another limitation of conventional imaging techniques is their failure to distinguish benign from malignant tumors. Also, cytology and histopathology cannot be employed as independent, sensitive tests to detect cancer at an early stage. With innovative molecular contrast media and materials, nanotechnology offers quicker and more accurate initial diagnosis, along with an ongoing assessment of cancer patient care [6].

Although nanoparticles are yet to be employed in actual cancer detection, they are currently being used in a range of medical screening tests. Gold nanoparticles are among the most commonly used in home test strips. A significant advantage of using nanoparticles for the detection of cancer is that they have a large surface area to volume ratio in comparison to their larger counterparts. This property ensures antibodies, aptamers, small molecules, fluorescent probes, polyethylene glycol (PEG), and other molecules cover the nanoparticle densely. This presents multiple binding ligands for cancer cells (multivalent effect of nanotools) and therefore increases the specificity and sensitivity of the bioassay [7,8]. Applications of nanotechnology in diagnosis are for the detection of extracellular biomarkers for cancer and for in vivo imaging. A good nanoprobe must have a long circulating time, specificity to the cancer tissue, and no toxicity to nearby tissue [9,10].

Detection of Biomarkers

Nanodevices have been studied to detect blood biomarkers and toxicity to healthy tissues nearby. These biomarkers include cancer-associated circulating tumor cells, associated proteins or cell surface proteins, carbohydrates or circulating tumor nucleic acids, and tumor-shed exosomes. Though it is well known that these biomarkers help to detect cancer at apreliminary stage, they also help to monitor the therapy and recurrence. They have limitations such as low concentrations in body fluids, variations in their levels and timings in different patients, and difficult prospective studies. These hurdles are overcome by nanotechnology, which offers high specificity and sensitivity. High sensitivity, specificity, and multiplexed measurements are all possible with nano-enabled sensors. To further illuminate a problem, next-generation gadgets combine capture with genetic analysis [11-15].

Imaging Using Nanotechnology

Nanotechnology uses nanoprobes that will accumulate selectively in tumor cells by passive or active targeting. The challenges faced are the interaction of nanoparticles with blood proteins, their clearance by the reticuloendothelial system, and targeting of tumors.Passive targeting suggests apreference for collecting the nanoparticles in the solid tumors due to extravasation from the blood vessels. This is made possible by the defective angiogenesis of the tumorwherein the new blood vessels do not have tight junctions in their endothelial cells and allow the leaking out of nanoparticles up to 150 nm in size, leading to a preferential accumulation of nanoparticles in the tumor tissue. This phenomenon is called enhanced permeability and retention (EPR).Active targeting involves the recognition of nanoparticles by the tumor cell surface receptors. This will enhance the sensitivity of in vivo tumor detection. For early detection of cancer, active targeting will give better results than passive targeting [16-18].

This can be classified as delivery of chemotherapy, immunotherapy, radiotherapy, and gene therapy, and delivery of chemotherapy is aimed at improving the pharmacokinetics and reducing drug toxicity by selective targeting and delivery to cancer tissues. This is primarily based on passive targeting, which employs the EPReffect described earlier [16]. Nanocarriers increase the half-life of the drugs. Immunotherapy is a promising new front in cancer treatment based on understanding the tumor-host interaction. Nanotechnology is being investigated to deliver immunostimulatory or immunomodulatory molecules. It can be used as an adjuvant to other therapies [19-21].

Role of Nanotechnology in Radiotherapy

Thistechnology involves targeted delivery of radioisotopes, targeted delivery of radiosensitizer, reduced side effects of radiotherapy by decreasing distribution to healthy tissues, and combining radiotherapy with chemotherapy to achieve synergism but avoid side effects, andadministering image-guided radiotherapy improves precision and accuracy while reducing exposure to surrounding normal tissues[22,23].

Gene Therapy Using Nanotechnology

There is a tremendous interest in the research in gene therapy for cancer, but the results are still falling short of clinical application. Despite a wide array of therapies aimed at gene modulation, such as gene silencing, anti-sense therapy, RNAinterference, and gene and genome editing, finding a way to deliver these effects is challenging. Nanoparticles are used as carriers for gene therapy, with advantages such as easy construction and functionalizing and low immunogenicity and toxicity. Gene-targeted delivery using nanoparticles has great future potential. Gene therapy is still in its infancy but is very promising [24].

Nanodelivery Systems

Quantum dots: Semiconductor nanocrystal quantum dots (QDs) have outstanding physical properties. Probes based on quantum dots have achieved promising cellular and in vivo molecular imaging developments. Increasing research is proving that technology based on quantum dots may become an encouraging approach in cancer research[4]. Biocompatible QDs were launched for mapping cancer cells in vitro in 1998. Scientists used these to create QD-based probes for cancer imaging that were conjugated with cancer-specific ligands, antibodies, or peptides. QD-immunohistochemistry (IHC) has more sensitivity and specificity than traditional immunohistochemistry (IHC) and can accomplish measurements of even low levels, offering considerably higher information for individualized management. Imaging utilizing quantum dots has emerged as a promising technology for early cancer detection[25,26].

Nanoshells and gold nanoparticles/gold nanoshells (AuNSs) are an excellent example of how combining nanoscience and biomedicine can solve a biological problem. They have an adjustable surface plasmon resonance, which can be set to the near-infrared to achieve optimal penetration of tissues. During laser irradiation, AuNSs' highly effective light-to-heat transition induces thermal destruction of the tumor without harming healthy tissues. AuNSs can even be used as a carrier for a wide range of diagnostic and therapeutic substances[27].

Dendrimers: These are novel nanoarchitectures with distinguishing characteristics such as a spherical three-dimensional shape, a monodispersed uni-micellar nature, and a nanometric size range. The biocompatibility of dendrimers has been employed to deliver powerful medications such as doxorubicin. This nanostructure targets malignant cells by attaching ligands to their surfaces. Dendrimers have been intensively investigated for targeting and delivering cancer therapeutics and magnetic resonance imaging contrast agents. The gold coating on its surface significantly reduced their toxicity without significantly affecting their size. It also served as an anchor for attaching high-affinity targeting molecules to tumor cells [28].

Liposomal nanoparticles (Figure 1): These have a role in delivery to a specific target spot, reducing biodistribution toxicity because of the surface-modifiable lipid composition, and have a structure similar to cell membranes. Liposome-based theranostics (particles constructed for the simultaneous delivery of therapeutic and diagnostic moieties) have the advantage of targeting specific cancer cells.Liposomes are more stable in the bloodstream and increase the solubility of the drug. They also act as sustained release preparations and protect the drug from degradation and pH changes, thereby increasing the drug's circulating half-life. Liposomes help to overcome multidrug resistance. Drugs such as doxorubicin, daunorubicin, mitoxantrone, paclitaxel, cytarabine, and irinotecanare used with liposome delivery [29-31].

Polymeric micelles: Micelles are usually spherical particles with a diameter of 10-100 nm, which are self-structured and have a hydrophilic covering shell and a hydrophobic core, suspended in an aqueous medium. Hydrophobic medicines can be contained in the micelle's core. A variety of molecules having the ability to bind to receptors, such as aptamers, peptides, antibodies, polysaccharides, and folic acid, are used to cover the surface of the micelle in active tumor cell targeting. Enzymes, ultrasound, temperature changes, pH gradients, and oxidationare used as stimuli in micelle drug delivery systems. Various physical and chemical triggers are used as stimuli in micelle drug delivery systems. pH-sensitive polymer micelle is released by lowering pH. A co-delivery system transports genetics, as well as anticancer medicines. Although paclitaxel is a powerful microtubule growth inhibitor, it has poor solubility, which causes fast drug aggregation and capillary embolisms. Such medicines' solubility can beraised to 0.0015-2 mg/ml by encapsulating them in micelles. Polymeric micelles are now being tested for use in nanotherapy [32].

Carbon nanotubes (CNTs): Carbon from burned graphite is used to create hollow cylinders known as carbon nanotubes (CNTs). They possess distinct physical and chemical characteristics that make them interesting candidates as carriers of biomolecules and drug delivery transporters. They have a special role in transporting anticancer drugs with a small molecular size. Wu et al. formed amedicine carrier system using multi-walled CNTs (MWCNTs) and the 10-hydroxycamptothecin (HCPT) anticancer compound. As a spacer between MWCNTs and HCPT, they employed hydrophilic diamine trimethylene glycol. In vitro and in vivo, their HCPT-MWCNT conjugates showed significantly increased anticancer efficacy when compared to traditional HCPTformulations. These conjugates were able to circulate in the blood longer and were collected precisely at the tumor site [33,34].

Limitations

Manufacturing costs, extensibility, safety, and the intricacy of nanosystems must all be assessed and balanced against possible benefits. The physicochemical properties of nanoparticles in biological systems determine their biocompatibility and toxicity. As a result, stringent manufacturing and delineation of nanomaterials for delivery of anticancer drugs are essential to reduce nanocarrier toxicity to surrounding cells. Another barrier to medication delivery is ensuring public health safety, as issues with nanoparticles do not have an immediate impact. The use of nanocarriers in cancer treatment may result in unforeseen consequences. Hypothetical possibilities of environmental pollution causing cardiopulmonary morbidity and mortality, production of reactive oxygen species causing inflammation and toxicity, and neuronal or dermal translocations are a few possibilities that worry scientists. Nanotoxicology, a branch of nanomedicine, has arisen as a critical topic of study, paving the way for evaluating nanoparticle toxicity [35-37].

Nanotechnology has been one of the recent advancements of science that not only has revolutionized the engineering field but also is now making its impact in the medical and paramedical field. Scientists have been successful in knowing the properties and characteristics of these nanomaterials and optimizing them for use in the healthcare industry. Although some nanoparticles have failed to convert to the clinic, other new and intriguing nanoparticles are now in research and show great potential, indicating that new treatment options may be available soon. Nanomaterials are highly versatile, with several benefits that can enhance cancer therapies and diagnostics.

These are particularly useful as drug delivery systems due to their tiny size and unique binding properties. Drugs such as doxorubicin, daunorubicin, mitoxantrone, paclitaxel, cytarabine, irinotecan, and amphotericin B are already being conjugated with liposomes for their delivery in current clinical practices. Doxorubicin, cytarabine, vincristine, daunorubicin, mitoxantrone, and paclitaxel, in particular, are key components of cancer chemotherapy. Even in the diagnosis of cancer for imaging and detection of tumor markers, particles such as nanoshells, dendrimers, and gold nanoparticles are currently in use.

Limitations of this novel technology include manufacturing expenses, extensibility, intricacy, health safety, and potential toxicity. These are being overcome adequately by extensive research and clinical trials, and nanomedicine is becoming one of the largest industries in the world. A useful collection of research tools and clinically practical gadgets will be made available in the near future thanks to advancements in nanomedicine. Pharmaceutical companies will use in vivo imaging, novel therapeutics, and enhanced drug delivery technologies in their new commercial applications. In the future, neuro-electronic interfaces and cell healing technology may change medicine and the medical industry when used to treat brain tumors.

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The Application of Nanotechnology and Nanomaterials in Cancer Diagnosis and Treatment: A Review - Cureus