Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration
Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration
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DOI：
10.1016/j.jconrel.2016.04.011
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发表时间：
2016-06-28
影响因子：
10.8
通讯作者：
Sobolev, Alexander S.
中科院分区：
文献类型：
--
作者：
Durymanov, Mikhail O.;Yarutkin, Alexey V.;Sobolev, Alexander S.
基于阳离子聚合物的制剂（聚合复合物）对肿瘤系统性基因递送的低效仍然是其临床转化的关键问题。在这里，我们表明，使用临床批准的药物调节肿瘤的生理状态可以改善静脉注射的复合物对具有不同特征的鼠黑色素瘤肿瘤的递送。不同作用机制药物的直接比较表明，硝酸甘油或氯沙坦的应用改善了多聚复合物纳米颗粒的外渗和肿瘤摄取，而血管紧张素II对多聚复合物在肿瘤组织中的积累和微分布几乎没有影响。根据肿瘤模型，硝酸甘油和氯沙坦的应用可使多聚复合物介导的基因递送功效提高 2 至 6 倍。根据肿瘤的生理状态，在肿瘤组织中的聚合复合物行为上获得的结果可能与优化聚合复合物和具有相似物理化学性质的其他纳米药物的递送相关。 (C) 2016 年由 Elsevier B.V. 出版
Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue. Application of nitroglycerin and losartan caused from 2- to 6-fold enhanced efficacy of polyplex-mediated gene delivery depending on the tumor model. The results obtained on polyplex behavior in tumor tissues depending on physiological state of the tumor can be relevant to optimize delivery of polyplexes and other nanomedicines with similar physicochemical properties. (C) 2016 Published by Elsevier B.V.