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Open AccessArticle

Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy

1
Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
2
Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA 19104, USA
3
Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 442; https://doi.org/10.3390/cancers11040442
Received: 17 February 2019 / Revised: 22 March 2019 / Accepted: 26 March 2019 / Published: 29 March 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
Non-viral, polymeric-based, siRNA nanoparticles (NPs) have been proposed as promising gene delivery systems. Encapsulating siRNA in targeted NPs could confer improved biological stability, extended half-life, enhanced permeability, effective tumor accumulation, and therapy. In this work, a peptide derived from apolipoprotein B100 (ApoB-P), the protein moiety of low-density lipoprotein, was used to target siRNA-loaded PEGylated NPs to the extracellular matrix/proteoglycans (ECM/PGs) of a mammary carcinoma tumor. siRNA against osteopontin (siOPN), a protein involved in breast cancer development and progression, was encapsulated into PEGylated poly(d,l-lactic-co-glycolic acid) (PLGA) NPs using the double emulsion solvent diffusion technique. The NPs obtained possessed desired physicochemical properties including ~200 nm size, a neutral surface charge, and high siOPN loading of ~5 µg/mg. ApoB-P-targeted NPs exhibited both enhanced binding to isolated ECM and internalization by MDA-MB-231 human mammary carcinoma cells, in comparison to non-targeted NPs. Increased accumulation of the targeted NPs was achieved in the primary mammary tumor of mice xenografted with MDA-MB-231 mammary carcinoma cells as well as in the lungs, one of the main sites affected by metastases. siOPN NPs treatment resulted in significant inhibition of tumor growth (similar bioactivity of both formulations), accompanied with significant reduction of OPN mRNA levels (~40% knockdown of mRNA levels). We demonstrated that targeted NPs possessed enhanced tumor accumulation with increased therapeutic potential in mice models of mammary carcinoma. View Full-Text
Keywords: nanoparticles; targeted delivery system; siRNA; osteopontin; mammary carcinoma nanoparticles; targeted delivery system; siRNA; osteopontin; mammary carcinoma
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MDPI and ACS Style

Ben-David-Naim, M.; Dagan, A.; Grad, E.; Aizik, G.; Nordling-David, M.M.; Morss Clyne, A.; Granot, Z.; Golomb, G. Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy. Cancers 2019, 11, 442.

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