School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, People's Republic of China.
Department of Neurology, Linyi People's Hospital, Linyi 276003, People's Republic of China.
Int J Nanomedicine. 2020 Aug 25;15:6451-6468. doi: 10.2147/IJN.S258906. eCollection 2020.
Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse.
The objective of this study was to construct a novel CPP modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG-MAL and CPP-PVGLIG-PEG, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration.
The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency.
CPP modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.
非小细胞肺癌（NSCLC）是最致命的癌症类型之一，具有高度浸润性。化疗远非令人满意，血管生成模拟（VM）和血管生成导致侵袭、迁移和复发。
本研究旨在构建一种新型 CPP 修饰的长春瑞滨和薯蓣皂素脂质体，采用两种新型功能材料 DSPE-PEG-MAL 和 CPP-PVGLIG-PEG，破坏 VM 通道、血管生成、上皮间质转化（EMT），抑制侵袭和迁移。
通过被动靶向，靶向脂质体可以在肿瘤部位富集，并且正电荷 CPP 在肿瘤微环境中过度表达的 MMP2 酶水解后暴露并通过静电吸附增强主动靶向。我们发现具有理想理化性质的 CPP 修饰的长春瑞滨和薯蓣皂素脂质体表现出增强的细胞摄取。体外和体内结果表明，CPP 修饰的长春瑞滨和薯蓣皂素脂质体可以抑制 A549 细胞的迁移和侵袭，破坏 VM 通道形成和血管生成，并阻断 EMT 过程。药效学研究表明，靶向脂质体在肿瘤部位有明显的蓄积，具有显著的抗肿瘤效率。
CPP 修饰的长春瑞滨加薯蓣皂素脂质体可为 NSCLC 提供新的治疗策略。
