Cancers, Vol. 11, Pages 442: Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy

Cancers, Vol. 11, Pages 442: Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy Cancers doi: 10.3390/cancers11040442 Authors: Meital Ben-David-Naim Arie Dagan Etty Grad Gil Aizik Mirjam M. Nordling-David Alisa Morss Clyne Zvi Granot Gershon Golomb 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 cell...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research