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A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma.

机译:一种基于EPR效应将基因递送至肿瘤的多功能包膜型纳米装置(MEND):一种克服PEG困境的策略。

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Gene and nucleic acid therapy are expected to play a major role in the next generation of medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel non-viral gene delivery system. Poly(ethylene glycol) (PEG)ylation is a useful method for achieving a longer circulation time for delivery of the MEND to a tumour via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity for the delivery system. For successful gene delivery for cancer treatment, the crucial issue associated with the use of PEG, the 'PEG dilemma' must be addressed. In this review, we describe the development and applications of MEND, and discuss strategies for overcoming the PEG dilemma, based on the manipulation of intracellular trafficking of cellular uptake and endosomal release using functional devices such as specific ligands, cleavable PEG systems and endosomal fusogenic/disruptic peptides.
机译:基因和核酸疗法有望在下一代医学中发挥重要作用。我们最近开发了一种多功能信封型纳米设备(MEND),用作新型非病毒基因递送系统。聚(乙二醇)(PEG)基化是一种有用的方法,可通过增强的通透性和保留(EPR)效应来实现更长的循环时间,以将MEND递送至肿瘤。然而,PEG化强烈抑制细胞摄取和内体逃逸,这导致递送系统的活性显着丧失。为了成功地将基因传递给癌症治疗,必须解决与使用PEG相关的关键问题,即“ PEG困境”。在这篇综述中,我们描述了MEND的开发和应用,并讨论了克服PEG困境的策略,它基于使用功能性设备(例如特定配体,可裂解PEG系统和内源性融合/破坏性肽。

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