Polycation-based nanoparticle delivery of RNAi therapeutics: Adverse effects and solutions

被引：130

作者：

Ballarin-Gonzalez, Borja ^{[1
]}

Howard, Kenneth Alan ^{[1
]}

机构：

[1] Univ Aarhus, Dept Mol Biol & Genet, Interdisciplinary Nanosci Ctr iNANO, Aarhus, Denmark

来源：

ADVANCED DRUG DELIVERY REVIEWS | 2012年 / 64卷 / 15期

关键词：

RNA interference; siRNA; Polycation; Nanoparticles; Polyplex; Toxicity; Immune stimulation; Chemical modifications; Biodistribution; DOUBLE-STRANDED-RNA; SMALL-INTERFERING RNA; TOLL-LIKE RECEPTOR-3; POLYELECTROLYTE COMPLEX MICELLES; PLASMACYTOID DENDRITIC CELLS; INNATE IMMUNE RECOGNITION; GENE SILENCING ACTIVITY; SHORT HAIRPIN RNAS; I-LIKE-RECEPTORS; RIG-I;

D O I：

10.1016/j.addr.2012.07.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical translation of RNAi-based drugs. Medical applications are dependent on safety; therefore, detailed investigation into potential toxicity to the cell or organism is required. This review addresses potential adverse effects arising from cellular and tissue interactions, immune stimulation and altered gene expression that can be associated with the assembled polyplex or the polycation and siRNA component parts. A greater understanding of the cellular mechanisms involved allows design-based solutions for rationale development of safe, effective and clinically relevant polyplex-based RNAi drugs. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：1717 / 1729

页数：13

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