Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prod | DDDT – Dove Medical Press

Yuan Hong,1 Shaomin Che,2 Beina Hui,2 Xiaoli Wang,2 Xiaozhi Zhang,2 Hailin Ma2

1Department of Medical Imaging, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China; 2Department of Oncology Radiotherapy, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China

Correspondence: Hailin MaDepartment of Oncology Radiotherapy, The First Affiliated Hospital of Xian Jiaotong University, No. 277 Yanta Xi Road, Xian, Shaanxi 710061, Peoples Republic of ChinaEmail mahlxjtu@sohu.com

Purpose: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CDDP) was used in combination with curcumin (CUR) for the treatment of non-small cell lung cancer. The aim of this study was to prepare and characterize CDDP prodrug and CUR co-encapsulated layer-by-layer nanoparticles (CDDP-PLGA/CUR LBL NPs) to induce cooperative response, maximize the therapeutic effect, overcome drug resistance, and reduce adverse side effects.Methods: CDDP prodrug (CDDP-PLGA) was synthesized. CDDP-PLGA/CUR LBL NPs were constructed and their physicochemical properties were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against human lung adenocarcinoma cell line (A549 cells) was investigated, and in vivo anti-tumor efficiency of CDDP-PLGA/CUR LBL NPs was evaluated on mice bearing A549 cell xenografts.Results: CDDP-PLGA/CUR LBL NPs have a size of 179.6 6.7 nm, a zeta potential value of 29.9 3.2 mV, high drug entrapment efficiency of 85.6 3.9% (CDDP) and 82.1 2.8% (CUR). The drug release of LBL NPs exhibited a sustained behavior, which made it an ideal vehicle for drug delivery. Furthermore, CDDP-PLGA/CUR LBL NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against A549 cells and lung cancer animal model compared to the single drug-loaded LBL NPs and free drug groups.Conclusion: CDDP-PLGA/CUR LBL NPs were reported for the first time in the combination therapy of lung cancer. The results demonstrated that the CDDP-PLGA/CUR LBL NPs might be a novel promising system for the synergetic treatment of lung carcinoma.

Keywords: lung cancer, combination therapy, layer-by-layer, cisplatin prodrug, curcumin

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