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

被引：539

作者：

Hatakeyama, Hiroto ^{[1
]}

Akita, Hidetaka ^{[1
]}

Harashima, Hideyoshi ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan

来源：

ADVANCED DRUG DELIVERY REVIEWS | 2011年 / 63卷 / 03期

关键词：

Gene delivery; MEND; PEG dilemma; Tumour targeting; Target ligand; PEG cleavage; Membrane fusion; TRANSFER IN-VITRO; INTRACELLULAR DELIVERY; TARGETED DELIVERY; MODIFIED LIPOSOMES; TRIGGERED RELEASE; LIPID PARTICLES; CARRIER SYSTEM; CANCER-THERAPY; DRUG-DELIVERY; DNA RELEASE;

D O I：

10.1016/j.addr.2010.09.001

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：152 / 160

页数：9

共 93 条

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