Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prodrug and Curcumin Co-Encapsulated Nanomedicine
Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prodrug and Curcumin Co-Encapsulated Nanomedicine
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DOI：
10.2147/dddt.s241291
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发表时间：
2020-01-01
影响因子：
4.8
通讯作者：
Ma, Hailin
中科院分区：
文献类型：
--
作者：
Hong, Yuan;Che, Shaomin;Ma, Hailin
目的：肺癌仍然是全球主要的癌症相关死亡。顺铂（CDDP）联合姜黄素（CUR）治疗非小细胞肺癌。本研究的目的是制备和表征CDDP前药和CUR共包封的层层纳米粒（CDDP-PLGA/CUR LBL NPs），以诱导协同反应，最大化治疗效果，克服耐药性，减少不良反应。构建了CDDP-PLGA/CUR LBL纳米粒，并通过粒径分析、Zeta电位测定、载药量、包封率和体外释药行为对其理化性质进行了研究。对人肺腺癌细胞系的体外细胞毒性研究了CDDP-PLGA/CUR LBL纳米粒对A549细胞异种移植物的抑制作用，并在携带A549细胞异种移植物的小鼠上评价了CDDP-PLGA/CUR LBL纳米粒的体内抗肿瘤效率。CDDP-PLGA/CUR LBL NP的尺寸为179.6 +/-6.7 nm，ζ电位值为-29.9 +/-3.2 mV，包封率为85.6 ± 3.9%（CDDP）和82.1 ± 2.8%（CUR）。LBL纳米粒的药物释放表现出持续的行为，这使其成为一种理想的药物递送载体。结论：CDDP-PLGA/CUR LBL NPs在肺癌的联合治疗中尚属首次报道。结果表明，CDDP-PLGA/CUR LBL纳米粒有望成为一种新型的肺癌协同治疗系统。
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.