Endoprotease-Mediated Intracellular Protein Delivery Using Nanocapsules

被引：95

作者：

Biswas, Anuradha ^{[2
,6
]}

Joo, Kye-Il ^{[5
]}

Liu, Jing ^{[4
]}

Zhao, Muxun ^{[2
,6
]}

Fan, Guoping ^{[4
]}

Wang, Pin ^{[5
]}

Gu, Zhen ^{[2
,3
,6
]}

Tang, Yi ^{[1
,2
,6
]}

机构：

[1] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[5] Univ So Calif, Mork Family Dept Chem Engn & Mat Sci, Los Angeles, CA 90089 USA

[6] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA

来源：

ACS NANO | 2011年 / 5卷 / 02期

关键词：

protein delivery; nanocapsule intracellular; polymer; endoprotease; POLY(ETHYLENE GLYCOL) HYDROGELS; GENE-EXPRESSION; CELL; FURIN; DNA; PEPTIDES; TRANSDUCTION; STABILITY; KLF4; NANOPARTICLES;

D O I：

10.1021/nn1031005

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Proteins possess distinct intracellular roles allowing them to have vast therapeutic applications. However, due to poor cellular permeability and fragility of most proteins, intracellular delivery of native, active proteins is challenging. We describe a biomimetic protein delivery vehicle which is degradable upon the digestion by furin, a ubiquitous Intracellular protease, to release encapsulated cargos. Proteins were encapsulated In a nanosized matrix prepared with monomers and a bisacrylated peptide cross-linker which can be specifically recognized and cleaved by furin. Release of encapsulated protein was confirmed in a cell-free system upon proteolytic degradation of nanocapsules. In vitro cell culture studies demonstrated successful intracellular delivery of both nuclear and cytosolic proteins and confirmed the importance of furin-degradable construction for native protein release. This endoprotease-mediated Intracellular delivery system may be extended to effectively deliver various biological therapeutics.

引用

页码：1385 / 1394

页数：10

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