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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy
Cancers, v 11(4), 442
29 Mar 2019
PMID: 30934857
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 similar to 200 nm size, a neutral surface charge, and high siOPN loading of similar to 5 mu g/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 (similar to 40% knockdown of mRNA levels). We demonstrated that targeted NPs possessed enhanced tumor accumulation with increased therapeutic potential in mice models of mammary carcinoma.
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Details
- Title
- Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy
- Creators
- Meital Ben-David-Naim - Hebrew University of JerusalemArie Dagan - Hebrew University of JerusalemEtty Grad - Hebrew University of JerusalemGil Aizik - Hebrew University of JerusalemMirjam M. Nordling-David - Hebrew University of JerusalemAlisa Morss Clyne - Drexel UniversityZvi Granot - Hebrew University of JerusalemGershon Golomb - Hebrew Univ Jerusalem, Fac Med, Inst Drug Res, IL-9112001 Jerusalem, Israel
- Publication Details
- Cancers, v 11(4), 442
- Publisher
- Mdpi
- Number of pages
- 18
- Grant note
- Yissum R&D of HUJI startup grants DREXEL-HUJI Project ISF 2648/16 / Israel Science Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:000467773400010
- Scopus ID
- 2-s2.0-85065305603
- Other Identifier
- 991021860700004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology