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肺癌联合化疗——利用适配体修饰的脂质-聚合物杂化纳米粒共递送多西他赛前药和顺铂。

Combination Chemotherapy of Lung Cancer - Co-Delivery of Docetaxel Prodrug and Cisplatin Using Aptamer-Decorated Lipid-Polymer Hybrid Nanoparticles.

机构信息

Department of Thoracic Surgery, Baoding No.1 Central Hospital, Baoding, Hebei Province, People's Republic of China.

Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Jun 9;14:2249-2261. doi: 10.2147/DDDT.S246574. eCollection 2020.

DOI:10.2147/DDDT.S246574
PMID:32606595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7293388/
Abstract

PURPOSE

Lung cancer is the leading cause of cancer mortality worldwide. Drug resistance is the major barrier for the treatment of non-small cell lung cancer (NSCLC). The aim of this research is to develop an aptamer-decorated hybrid nanoparticle for the co-delivery of docetaxel prodrug (DTXp) and cisplatin (DDP) and to treat lung cancer.

MATERIALS AND METHODS

Aptamer-conjugated lipid-polymer ligands and redox-sensitive docetaxel prodrug were synthesized. DTXp and DDP were loaded into the lipid-polymer hybrid nanoparticles (LPHNs). The targeted efficiency of aptamer-decorated, DTXp and DDP co-encapsulated LPHNs (APT-DTXp/DDP-LPHNs) was determined by performing a cell uptake assay by flow cytometry-based analysis. In vivo biodistribution and anticancer efficiency of APT-DTXp/DDP-LPHNs were evaluated on NSCLC-bearing mice xenograft.

RESULTS

APT-DTXp/DDP-LPHNs had a particle size of 213.5 ± 5.3 nm, with a zeta potential of 15.9 ± 1.9 mV. APT-DTXp/DDP-LPHNs exhibited a significantly enhanced cytotoxicity (drug concentration causing 50% inhibition was 0.71 ± 0.09 μg/mL), synergy antitumor effect (combination index was 0.62), and profound tumor inhibition ability (tumor inhibition ratio of 81.4%) compared with the non-aptamer-decorated LPHNs and single drug-loaded LPHNs.

CONCLUSION

Since the synergistic effect of the drugs was found in this system, it would have great potential to inhibit lung tumor cells and in vivo tumor growth.

摘要

目的

肺癌是全球癌症死亡的主要原因。耐药性是治疗非小细胞肺癌（NSCLC）的主要障碍。本研究旨在开发一种适体修饰的杂化纳米粒子，用于共递送多西他赛前药（DTXp）和顺铂（DDP）并治疗肺癌。

材料和方法

合成了适体偶联的脂质-聚合物配体和氧化还原敏感的多西他赛前药。将 DTXp 和 DDP 载入脂质-聚合物杂化纳米粒子（LPHN）中。通过基于流式细胞术的细胞摄取分析来确定适体修饰、DTXp 和 DDP 共包封的 LPHN（APT-DTXp/DDP-LPHN）的靶向效率。在 NSCLC 荷瘤小鼠异种移植模型上评估 APT-DTXp/DDP-LPHN 的体内分布和抗癌效率。

结果

APT-DTXp/DDP-LPHN 的粒径为 213.5 ± 5.3nm，zeta 电位为 15.9 ± 1.9mV。APT-DTXp/DDP-LPHN 表现出显著增强的细胞毒性（引起 50%抑制的药物浓度为 0.71 ± 0.09μg/mL）、协同抗肿瘤作用（组合指数为 0.62）和深刻的肿瘤抑制能力（肿瘤抑制率为 81.4%），与非适体修饰的 LPHN 和单药载药 LPHN 相比。

结论

由于在该系统中发现了药物的协同作用，因此它具有抑制肺肿瘤细胞和体内肿瘤生长的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/198ac78edc87/DDDT-14-2249-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/198ac78edc87/DDDT-14-2249-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/8cfa56ada486/DDDT-14-2249-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/698476f501c0/DDDT-14-2249-g0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/94151659595b/DDDT-14-2249-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/9656595dc0ae/DDDT-14-2249-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/1a5d7f5b0178/DDDT-14-2249-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3003/7293388/198ac78edc87/DDDT-14-2249-g0008.jpg

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