Hyaluronic acid-coated PEI-PLGA nanoparticles mediated co-delivery of doxorubicin and miR-542-3p for triple negative breast cancer therapy.

Abstract

MicroRNAs (miRNAs) play critical roles in modulating the oncogenic driver pathways involved in the acquisition of resistance to cancer treatments. MiR-542-3p serves as a potent tumor suppressor molecule by targeting tumor suppressor p53 and apoptosis inhibitor survivin. A hyaluronic acid (HA)-decorated polyethylenimine-poly(d,l-lactide-co-glycolide) (PEI-PLGA) nanoparticle system was developed in this study for targeted co-delivery of doxorubicin (DOX) and miR-542-3p for triple negative breast cancer (TNBC) therapy. This system showed an average size at 131.7 nm and high drug encapsulation efficiency, and prevented miR-542-3p degradation in the serum. HA/PEI-PLGA nanoparticles increased both drug uptake and cytotoxicity in MDA-MB-231 cells compared to MCF-7 cells, which express lower CD44 levels. Intracellular restoration of miR-542-3p further promoted TNBC cell apoptosis via activating p53 and inhibiting survivin expression. These results indicate that HA/PEI-PLGA nanoparticles have the potential to co-deliver chemotherapeutic agents and tumor suppressive miRNAs in combinatorial TNBC therapy.

FROM THE CLINICAL EDITOR:

Breast cancer is a leading cause of mortality in women worldwide. The so-called triple negative tumors for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) usually signifies poor prognosis. In this article, the authors developed a hyaluronic acid (HA)-decorated polyethylenimine-poly(D,L-lactide-co-glycolide) (PEI-PLGA) nanoparticle system for the delivery of both doxorubicin (DOX) and miR-542-3p against this tumor sub-type. This may represent a promising new therapy to treat breast cancer patients in the near future.

• Authors: Shengpeng Wang, Jinming Zhang, Yitao Wang, Meiwan Chen
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 12 Issue 2 Pg. 411-20 (Feb 2016) ISSN: 1549-9642 [Electronic] United States
• PMID: 26711968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• MIRN542 microRNA, human
• MicroRNAs
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Doxorubicin
• Polyethyleneimine
• Hyaluronic Acid

Topics

• Antibiotics, Antineoplastic (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Breast (drug effects, metabolism, pathology)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, pharmacology)
• Drug Carriers (chemistry)
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Therapy
• Humans
• Hyaluronic Acid (chemistry)
• Lactic Acid (chemistry)
• MicroRNAs (administration & dosage, pharmacology)
• Nanoparticles (chemistry)
• Polyethyleneimine (chemistry)
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Triple Negative Breast Neoplasms (genetics, pathology, therapy)