Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prodrug and Curcumin Co-Encapsulated Nanomedicine

• Published in: Drug design, development and therapy development and therapy, 2020-01, Vol.14, p.2263-2274
• Main Authors: Hong, Yuan, Che, Shaomin, Hui, Beina, Wang, Xiaoli, Zhang, Xiaozhi, Ma, Hailin
• Format: Article
• Language: English
• Subjects: A549 Cells; Analysis; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; B cells; Cancer treatment; Capsules - chemistry; Capsules - pharmacology; Cisplatin; Cisplatin - chemistry; Cisplatin - pharmacology; cisplatin prodrug; combination therapy; Combined Modality Therapy; curcumin; Curcumin - chemistry; Curcumin - pharmacology; Drug delivery systems; Drug Liberation; Drug resistance; Health aspects; Humans; layer-by-layer; lung cancer; Lung Neoplasms - drug therapy; Molecular Structure; Nanomedicine; Non-small cell lung cancer; Original Research; Particle Size; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; Respiratory system agents; Surface Properties
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S241291

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. 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. 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. 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.