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Enhanced delivery of PEAL nanoparticles with ultrasound targeted microbubble destruction mediated siRNA transfection in human MCF-7/S and MCF-7/ADR cells in vitro

Authors Teng Y, Bai M, Sun Y, Wang Q, Li F, Xing J, Du L, Gong T, Duan Y

Received 19 January 2015

Accepted for publication 22 April 2015

Published 27 August 2015 Volume 2015:10(1) Pages 5447—5457

DOI https://doi.org/10.2147/IJN.S81172

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Lei Yang

Yanwei Teng,1,2,* Min Bai,3,* Ying Sun,2 Qi Wang,1,2 Fan Li,3 Jinfang Xing,3 Lianfang Du,3 Tao Gong,1 Yourong Duan2

1Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 3Department of Ultrasound, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: The gene knockdown activity of small interfering RNA (siRNA) has led to their use as potential therapeutics for a variety of diseases. However, successful gene therapy requires safe and efficient delivery systems. In this study, we choose mPEG-PLGA-PLL nanoparticles (PEAL NPs) with ultrasound targeted microbubble destruction (UTMD) to efficiently deliver siRNA into cells. An emulsification-solvent evaporation method was used to prepare siRNA-loaded PEAL NPs. The NPs possessed an average size of 132.6±10.3 nm (n=5), with a uniform spherical shape, and had an encapsulation efficiency (EE) of more than 98%. As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations. The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells. Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

Keywords: gene delivery, mPEG-PLGA-PLL, UTMD, emulsification-solvent evaporation method, orthogonal design

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