Back to Journals » International Journal of Nanomedicine » Volume 7

A novel polyethyleneimine-coated adeno-associated virus-like particle formulation for efficient siRNA delivery in breast cancer therapy: preparation and in vitro analysis

Authors Shao W, Paul A, Abbasi S, Chahal PS, Mena JA, Montes J, Kamen A, Prakash S

Received 6 October 2011

Accepted for publication 30 October 2011

Published 23 March 2012 Volume 2012:7 Pages 1575—1586

DOI https://doi.org/10.2147/IJN.S26891

Review by Single-blind

Peer reviewer comments 2

Wei Shao1, Arghya Paul1, Sana Abbasi1, Parminder S Chahal2, Jimmy A Mena2, Johnny Montes2, Amine Kamen2, Satya Prakash1

1Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 2Animal Cell Technology, Bioprocess Centre, Biotechnology Research Institute, National Research Council, Montreal, Quebec, Canada

Background: Systemic delivery of small interfering RNA (siRNA) is limited by its poor stability and limited cell-penetrating properties. To overcome these limitations, we designed an efficient siRNA delivery system using polyethyleneimine-coated virus-like particles derived from adeno-associated virus type 2 (PEI-AAV2-VLPs).
Methods: AAV2-VLPs were produced in insect cells by infection with a baculovirus vector containing three AAV2 capsid genes. Using this method, we generated well dispersed AAV2-VLPs with an average diameter of 20 nm, similar to that of the wild-type AAV2 capsid. The nanoparticles were subsequently purified by chromatography and three viral capsid proteins were confirmed by Western blot. The negatively charged AAV2-VLPs were surface-coated with PEI to develop cationic nanoparticles, and the formulation was used for efficient siRNA delivery under optimized transfection conditions.
Results: PEI-AAV2-VLPs were able to condense siRNA and to protect it from degradation by nucleases, as confirmed by gel electrophoresis. siRNA delivery mediated by PEI-AAV2-VLPs resulted in a high transfection rate in MCF-7 breast cancer cells with no significant cytotoxicity. A cell death assay also confirmed the efficacy and functionality of this novel siRNA formulation towards MCF-7 cancer cells, in which more than 60% of cell death was induced within 72 hours of transfection.
Conclusion: The present study explores the potential of virus-like particles as a new approach for gene delivery and confirms its potential for breast cancer therapy.

Keywords: adeno-associated virus type 2, virus-like particles, small interfering RNA delivery, breast cancer therapy, nanomedicine

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

Malhotra M, Tomaro-Duchesneau C, Saha S, Kahouli I, Prakash S

International Journal of Nanomedicine 2013, 8:2041-2052

Published Date: 21 May 2013

Gut microbiota: next frontier in understanding human health and development of biotherapeutics

Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C

Biologics: Targets and Therapy 2011, 5:71-86

Published Date: 11 July 2011

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

Bhathena J, Kulamarva A, Martoni C, Urbanska A, Malhotra M,  Paul A, Prakash S

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2011, 4:195-203

Published Date: 3 June 2011

A novel method for synthesizing PEGylated chitosan nanoparticles: strategy, preparation, and in vitro analysis

Meenakshi Malhotra, Ciaran Lane, Catherine Tomaro-Duchesneau, et al

International Journal of Nanomedicine 2011, 6:485-494

Published Date: 3 March 2011

Potentials and limitations of microorganisms as renal failure biotherapeutics

Poonam Jain, Sapna Shah, Razek Coussa, Satya Prakash

Biologics: Targets and Therapy 2009, 3:233-243

Published Date: 18 May 2009

Methods, potentials, and limitations of gene delivery to regenerate central nervous system cells

Arvind Kumar, Tryambak D Singh, Santosh K Singh, Satya Prakash

Biologics: Targets and Therapy 2009, 3:245-256

Published Date: 15 May 2009

Colon-targeted delivery of live bacterial cell biotherapeutics including microencapsulated live bacterial cells

Satya Prakash, Aleksandra Malgorzata Urbanska

Biologics: Targets and Therapy 2008, 2:355-378

Published Date: 12 September 2008

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Retraction

Cárdenas WH, Mamani JB, Sibov TT, Caous CA, Amaro E Jr, Gamarra LF

International Journal of Nanomedicine 2012, 7:5107-5108

Published Date: 21 September 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Antibiofilm surface functionalization of catheters by magnesium fluoride nanoparticles

Lellouche J, Friedman A, Lahmi R, Gedanken A, Banin E

International Journal of Nanomedicine 2012, 7:1175-1188

Published Date: 1 March 2012

Servant leadership: a case study of a Canadian health care innovator

Vanderpyl TH

Journal of Healthcare Leadership 2012, 4:9-16

Published Date: 16 February 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010