title: 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.
  
  
  BACKGROUND
  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.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China. Electronic address: ytwang@umac.mo.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China. Electronic address: mwchen@umac.mo.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D035683:MicroRNAs / Q000008:administration & dosage* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; C572357:MIRN542 microRNA, human; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D011094:Polyethyleneimine; D006820:Hyaluronic Acid
keywords: Apoptosis; Breast cancer; Doxorubicin; Hyaluronic acid; MicroRNA