Shedding PEG Palisade by Temporal Photostimulation and Intracellular Reducing Milieu for Facilitated Intracellular Trafficking and DNA Release
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- 作者：Tieyan Wang ; Qixian Chen ; Hongguang Lu ; Wei Li ; Zaifen Li ; Jianbiao Ma ; Hui Gao
- 刊名：Bioconjugate Chemistry
- 出版年：2016
- 出版时间：August 17, 2016
- 年：2016
- 卷：27
- 期：8
- 页码：1949-1957
- 全文大小：471K
- 年卷期：0
- ISSN：1520-4812
文摘
The dilemma of poly(ethylene glycol) surface modification (PEGylation) inspired us to develop an intracellularly sheddable PEG palisade for synthetic delivery systems. Here, we attempted to conjugate PEG to polyethylenimine (PEI) through tandem linkages of disulfide-bridge susceptible to cytoplasmic reduction and an azobenzene/cyclodextrin inclusion complex responsive to external photoirradiation. The subsequent investigations revealed that facile PEG detachment could be achieved in endosomes upon photoirradiation, consequently engendering exposure of membrane-disruptive PEI for facilitated endosome escape. The liberated formulation in the cytosol was further subjected to complete PEG detachment relying on disulfide cleavage in the reductive cytosol, thus accelerating dissociation of electrostatically assembled PEI/DNA polyplex to release DNA by means of polyion exchange reaction with intracellularly charged species, ultimately contributing to efficient gene expression.