PMID- 30934857
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231011
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 4
DP  - 2019 Mar 29
TI  - Targeted siRNA Nanoparticles for Mammary Carcinoma Therapy.
LID - 10.3390/cancers11040442 [doi]
LID - 442
AB  - 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 microg/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.
FAU - Ben-David-Naim, Meital
AU  - Ben-David-Naim M
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. meitalben@ekmd.huji.ac.il.
FAU - Dagan, Arie
AU  - Dagan A
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. daganarie@gmail.com.
FAU - Grad, Etty
AU  - Grad E
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. ettyg@ekmd.huji.ac.il.
FAU - Aizik, Gil
AU  - Aizik G
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. gil.aizik@gmail.com.
FAU - Nordling-David, Mirjam M
AU  - Nordling-David MM
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. mirjamd@ekmd.huji.ac.il.
FAU - Morss Clyne, Alisa
AU  - Morss Clyne A
AD  - Department of Mechanical Engineering and Mechanics, Drexel University, 
      Philadelphia, PA 19104, USA. alisam@coe.drexel.edu.
FAU - Granot, Zvi
AU  - Granot Z
AD  - Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew 
      University of Jerusalem, Jerusalem 9112001, Israel. zvikag@ekmd.huji.ac.il.
FAU - Golomb, Gershon
AU  - Golomb G
AUID- ORCID: 0000-0002-7369-9831
AD  - Institute for Drug Research, Faculty of Medicine, The Hebrew University of 
      Jerusalem, Jerusalem 9112001, Israel. gershong@ekmd.huji.ac.il.
LA  - eng
PT  - Journal Article
DEP - 20190329
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6521050
OTO - NOTNLM
OT  - mammary carcinoma
OT  - nanoparticles
OT  - osteopontin
OT  - siRNA
OT  - targeted delivery system
COIS- The authors declare no conflict of interest.
EDAT- 2019/04/03 06:00
MHDA- 2019/04/03 06:01
PMCR- 2019/03/29
CRDT- 2019/04/03 06:00
PHST- 2019/02/17 00:00 [received]
PHST- 2019/03/22 00:00 [revised]
PHST- 2019/03/26 00:00 [accepted]
PHST- 2019/04/03 06:00 [entrez]
PHST- 2019/04/03 06:00 [pubmed]
PHST- 2019/04/03 06:01 [medline]
PHST- 2019/03/29 00:00 [pmc-release]
AID - cancers11040442 [pii]
AID - cancers-11-00442 [pii]
AID - 10.3390/cancers11040442 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Mar 29;11(4):442. doi: 10.3390/cancers11040442.