Targeted siRNA nanoparticles for mammary carcinoma therapy

Meital Ben-David-Naim, Arie Dagan, Etty Grad, Gil Aizik, Mirjam M. Nordling-David, A. M. Clyne, Zvi Granot, Gershon Golomb

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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).

Original languageEnglish
Article number442
Issue number4
StatePublished - 29 Mar 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.


Funding: This study was supported in part by the DREXEL—HUJI Project (A.M.C. & G.G.), the Israel Science Foundation (ISF 2648/16; G.G.), and Yissum R&D of HUJI startup grants (G.G.).

FundersFunder number
Israel Science FoundationISF 2648/16


    • Mammary carcinoma
    • Nanoparticles
    • Osteopontin
    • SiRNA
    • Targeted delivery system


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