Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery

JOURNAL OF CONTROLLED RELEASE

卷:152

Article

Coue, Gregory¹  Engbersen, Johan F. J.¹ 

[1] Univ Twente, Dept Biomed Chem, MIRA Inst Biomed Technol & Tech Med, Fac Sci & Technol, NL-7500 AE Enschede, Netherlands

关键词: Bioreducible polymers;    Disulfide reduction;    Intracellular protein delivery;    Poly(amidoamine);    Polyelectrolyte complex;   

DOI  :  10.1016/j.jconrel.2011.01.023

来源: Elsevier

【 摘 要 】

An effective intracellular protein delivery system was developed based on functionalized linear poly (amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Three differently functionalized PAAs were synthesized, two of these having repetitive disulfide bonds in the main chain, by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to cystamine bisacrylamide (CBA), histamine (HIS) to CBA, and ABOL to bis(acryloyl)piperazine (BAP). These water-soluble PAAs efficiently condense beta-galactosidase by self-assembly into nanoscaled and positively-charged complexes. Stable under neutral extracellular conditions, the disulfide-containing nanocomplexes rapidly destabilized in a reductive intracellular environment. Cell-internalization and cytotoxicity experiments showed that the PAA-based nanocomplexes were essentially non-toxic. beta-Galactosidase was successfully internalized into cells, with up to 94% of the cells showing beta-galactosidase activity, whereas the enzyme alone was not taken up by the cells. The results indicate that these poly(amidoamine)s have excellent properties as highly potent and non-toxic intracellular protein carriers, which should create opportunities for novel applications in protein delivery. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free