title: Orlistat and antisense-miRNA-loaded PLGA-PEG nanoparticles for enhanced triple negative breast cancer therapy.
abstract: BACKGROUND
  This study explores the use of hydrophilic poly(ethylene glycol)-conjugated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NPs) as delivery system to improve the antitumor effect of antiobesity drug orlistat for triple-negative breast cancer (TNBC) therapy by improving its bioavailability.
  
  
  METHODS
  PLGA-PEG-NPs were synthesized by emulsion-diffusion-evaporation method, and the experiments were conducted in vitro in MDA-MB-231 and SKBr3 TNBC and normal breast fibroblast cells.
  
  
  RESULTS
  Delivery of orlistat via PLGA-PEG-NPs reduced its IC50 compared with free orlistat. Combined treatment of orlistat-loaded NPs and doxorubicin or antisense-miR-21-loaded NPs significantly enhanced apoptotic effect compared with independent doxorubicin, anti-miR-21-loaded NPs, orlistat-loaded NPs or free orlistat treatments.
  
  
  CONCLUSIONS
  We demonstrate that orlistat in combination with antisense-miR-21 or current chemotherapy holds great promise as a novel and versatile treatment agent for TNBC.
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Aarohi
authors.initials: A
authors.lastname: Bhargava-Shah
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Kira
authors.initials: K
authors.lastname: Foygel
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Rammohan
authors.initials: R
authors.lastname: Devulapally
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
mesh_terms: D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D007783:Lactones / Q000008:administration & dosage*; D000077403:Orlistat; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016372:RNA, Antisense / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000008:administration & dosage*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D007783:Lactones; D016372:RNA, Antisense; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077403:Orlistat
keywords: PLGA nanoparticles; TNBC; anti-miR; cancer therapy; orlistat