Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Department of Oncology Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Drug Des Devel Ther. 2020 Jun 9;14:2263-2274. doi: 10.2147/DDDT.S241291. eCollection 2020.
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.
肺癌仍是全球导致癌症相关死亡的主要原因。顺铂（CDDP）与姜黄素（CUR）联合用于治疗非小细胞肺癌。本研究旨在制备和表征 CDDP 前药和 CUR 共包封的层层纳米粒子（CDDP-PLGA/CUR LBL NPs），以诱导协同反应，最大限度地提高治疗效果，克服耐药性，并减少不良反应。
合成 CDDP 前药（CDDP-PLGA）。构建 CDDP-PLGA/CUR LBL NPs，并通过粒径分析、Zeta 电位测量、药物载量、药物包封效率和体外药物释放行为进行研究。研究了对人肺腺癌细胞系（A549 细胞）的体外细胞毒性，并在荷 A549 细胞异种移植瘤的小鼠中评估了 CDDP-PLGA/CUR LBL NPs 的体内抗肿瘤效率。
CDDP-PLGA/CUR LBL NPs 的粒径为 179.6±6.7nm，Zeta 电位值为-29.9±3.2mV，药物包封效率高，CDDP 为 85.6±3.9%，CUR 为 82.1±2.8%。LBL NPs 的药物释放呈现出持续的行为，使其成为一种理想的药物递送载体。此外，与单载药 LBL NPs 和游离药物组相比，CDDP-PLGA/CUR LBL NPs 能显著增强体外细胞毒性和体内对 A549 细胞和肺癌动物模型的抗肿瘤作用。
首次报道了 CDDP-PLGA/CUR LBL NPs 在肺癌联合治疗中的应用。结果表明，CDDP-PLGA/CUR LBL NPs 可能是一种治疗肺癌的新型有前途的系统。
