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Combination Therapy of Lung Cancer Using Layer-by-Layer Cisplatin Prodrug and Curcumin Co-Encapsulated Nanomedicine.
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-06-09 , DOI: 10.2147/dddt.s241291 Yuan Hong 1 , Shaomin Che 2 , Beina Hui 2 , Xiaoli Wang 2 , Xiaozhi Zhang 2 , Hailin Ma 2
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-06-09 , DOI: 10.2147/dddt.s241291 Yuan Hong 1 , Shaomin Che 2 , Beina Hui 2 , Xiaoli Wang 2 , Xiaozhi Zhang 2 , Hailin Ma 2
Affiliation
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
中文翻译：
层层顺铂前药与姜黄素共包封纳米药物联合治疗肺癌。
目的：肺癌仍然是全球主要的癌症相关死亡。顺铂（CDDP）与姜黄素（CUR）联合用于治疗非小细胞肺癌。本研究的目的是制备和表征 CDDP 前药和 CUR 共包封的逐层纳米粒子 (CDDP-PLGA/CUR LBL NPs)，以诱导协同反应、最大化治疗效果、克服耐药性并减少不良反应。效果。
方法：合成了 CDDP 前药 (CDDP-PLGA)。构建了CDDP-PLGA/CUR LBL NPs，并通过粒度分析、zeta电位测量、载药量、药物包封率和体外药物释放行为研究了它们的理化性质。研究了对人肺腺癌细胞系（A549 细胞）的体外细胞毒性，并在携带 A549 细胞异种移植物的小鼠身上评估了 CDDP-PLGA/CUR LBL NPs 的体内抗肿瘤效率。
结果：CDDP-PLGA/CUR LBL NPs 的尺寸为 179.6 ± 6.7 nm，zeta 电位值为 - 29.9 ± 3.2 mV，药物包封率高达 85.6 ± 3.9% (CDDP) 和 82.1 ± 2.8% (CUR)。LBL NPs 的药物释放表现出持续的行为，这使其成为药物输送的理想载体。此外，与单一载药 LBL NPs 和游离药物组相比，CDDP-PLGA/CUR LBL NPs 可以显着增强对 A549 细胞和肺癌动物模型的体外细胞毒性和体内抗肿瘤作用。
结论： CDDP-PLGA/CUR LBL NPs在肺癌联合治疗中的报道尚属首次。结果表明，CDDP-PLGA/CUR LBL NPs可能是一种用于肺癌协同治疗的新型有前景的系统。
关键词：肺癌, 联合治疗, 逐层, 顺铂前药, 姜黄素
更新日期：2020-06-09
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
中文翻译：
层层顺铂前药与姜黄素共包封纳米药物联合治疗肺癌。
目的：肺癌仍然是全球主要的癌症相关死亡。顺铂（CDDP）与姜黄素（CUR）联合用于治疗非小细胞肺癌。本研究的目的是制备和表征 CDDP 前药和 CUR 共包封的逐层纳米粒子 (CDDP-PLGA/CUR LBL NPs)，以诱导协同反应、最大化治疗效果、克服耐药性并减少不良反应。效果。
方法：合成了 CDDP 前药 (CDDP-PLGA)。构建了CDDP-PLGA/CUR LBL NPs，并通过粒度分析、zeta电位测量、载药量、药物包封率和体外药物释放行为研究了它们的理化性质。研究了对人肺腺癌细胞系（A549 细胞）的体外细胞毒性，并在携带 A549 细胞异种移植物的小鼠身上评估了 CDDP-PLGA/CUR LBL NPs 的体内抗肿瘤效率。
结果：CDDP-PLGA/CUR LBL NPs 的尺寸为 179.6 ± 6.7 nm，zeta 电位值为 - 29.9 ± 3.2 mV，药物包封率高达 85.6 ± 3.9% (CDDP) 和 82.1 ± 2.8% (CUR)。LBL NPs 的药物释放表现出持续的行为，这使其成为药物输送的理想载体。此外，与单一载药 LBL NPs 和游离药物组相比，CDDP-PLGA/CUR LBL NPs 可以显着增强对 A549 细胞和肺癌动物模型的体外细胞毒性和体内抗肿瘤作用。
结论： CDDP-PLGA/CUR LBL NPs在肺癌联合治疗中的报道尚属首次。结果表明，CDDP-PLGA/CUR LBL NPs可能是一种用于肺癌协同治疗的新型有前景的系统。
关键词：肺癌, 联合治疗, 逐层, 顺铂前药, 姜黄素
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