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pH-sensitive degradable nanoparticles for highly efficient intracellular delivery of exogenous protein

Authors Xu D, Wu F, Chen Y, Wei L, Yuan W

Received 6 May 2013

Accepted for publication 8 June 2013

Published 2 September 2013 Volume 2013:8(1) Pages 3405—3414

DOI https://doi.org/10.2147/IJN.S47701

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Dan Xu,1 Fei Wu,1 Yinghui Chen,2,* Liangming Wei,3,* Weien Yuan1,*

1School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 2Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, 3Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, People's Republic of China

*These authors contributed equally to this work

Background: Encapsulating exogenous proteins into a nanosized particulate system for delivery into cells is a great challenge. To address this issue, we developed a novel nanoparticle delivery method that differs from the nanoparticles reported to date because its core was composed of cross-linked dextran glassy nanoparticles which had pH in endosome-responsive environment and the protein was loaded in the core of cross-linked dextran glassy nanoparticles.
Methods: In this study, dextran in a poly(ethylene glycol) aqueous two-phase system created a different chemical environment in which proteins were encapsulated very efficiently (84.3% and 89.6% for enhanced green fluorescent protein and bovine serum albumin, respectively) by thermodynamically favored partition. The structures of the nanoparticles were confirmed by confocal laser scanning microscopy and scanning electron microscopy.
Results: The nanoparticles had a normal size distribution and a mean diameter of 186 nm. MTT assays showed that the nanoparticles were nontoxic up to a concentration of 2000 µg/mL in human hepatocarcinoma cell line SMMC-7721, HeLa, and BRL-3A cells. Of note, confocal laser scanning microscopy studies showed that nanoparticles loaded with fluorescein isothiocyanate-bovine serum albumin were efficiently delivered and released proteins into the cytoplasm of HeLa cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that nanoparticles with a functional protein (apoptin) efficiently induced significant tumor cell apoptosis, which was confirmed by DAPI staining.
Conclusion: Our findings indicate that these nanoparticles meet the high demands for delivering protein medicines and have great potential in protein therapy.

Keywords: cellular uptake, protein delivery, nanoparticles, apoptosis

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