Background: 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.
Purpose: The objective of this study was to construct a novel CPP _(mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG₂₀₀₀-MAL and CPP-PVGLIG-PEG₅₀₀₀, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration.
Methods and Results: 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 _(mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP _(mmp) 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.
Conclusion: CPP _(mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.



中文翻译：

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同时封装生物和化疗药物的肿瘤微环境响应脂质体增强非小细胞肺癌的抗肿瘤功效。


背景：非小细胞肺癌（NSCLC）是最致命的高度浸润性癌症之一。化疗远不能令人满意，血管生成拟态（VM）和血管生成导致侵袭、迁移和复发。

目的：本研究的目的是通过两种新型功能材料DSPE-PEG ₂₀₀₀ -MAL和CPP-PVGLIG-PEG ₅₀₀₀构建新型CPP _（mmp）修饰的长春瑞滨和薯蓣皂苷脂质体，以破坏VM通道、血管生成、EMT和抑制侵袭和迁移。

方法与结果：靶向脂质体可通过被动靶向富集于肿瘤部位，带正电荷的CPP被肿瘤微环境中过表达的MMP2酶水解后暴露出来，通过静电吸附增强主动靶向。我们发现CPP _（mmp）修饰的长春瑞滨和薯蓣皂苷脂质体具有理想的理化性质，并表现出增强的细胞摄取。体内外结果表明，CPP _（mmp）修饰的长春瑞滨和薯蓣皂苷脂质体可抑制A549细胞的迁移和侵袭，破坏VM通道形成和血管生成，阻断EMT过程。药效学研究表明，靶向脂质体在肿瘤部位具有明显的蓄积作用，具有良好的抗肿瘤效果。

结论： CPP _（mmp）修饰的长春瑞滨联合薯蓣皂苷脂质体可为NSCLC提供新的治疗策略。