title: Oleanolic acid-loaded PLGA-TPGS nanoparticles combined with heparin sodium-loaded PLGA-TPGS nanoparticles for enhancing chemotherapy to liver cancer.
abstract: OBJECTIVE
  Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as sustained and targeted delivery carriers and combined with oleanolic acid (OA)-loaded PLGA-TPGS nanoparticles (OPTNs) that had been investigated in our previous work to form a combination therapy system for the treatment of liver cancer.
  
  
  METHODS
  To inspect cellular uptake and evaluate liver-targeting performance by analysing drug concentrations and cryosections, fluorescent probe coumarin-6 and eosin was used in preparations of HS/eosin-loaded, HS/coumarin-6-loaded, and OA/coumarin-6-loaded PLGA-TPGS nanoparticles. All of these NPs were characterized in terms of size, size distribution, surface charge, drug loading, encapsulation efficiency, and in vitro release profile. The apoptosis of HepG2 cells induced by OPTNs combined with HPTNs was determined by Annexin V-FITC staining and PI labelling.
  
  
  RESULTS
  Transmission electron microscopy indicated that all of the nanoparticles were stably dispersed spheres with diameters ranging from 100 to 200nm. The results demonstrated that fluorescent nanoparticles were efficiently internalized into HepG2 and HCa-F cells, and that they exhibited enhanced liver targeting. The combination of HPTNs and OPTNs resulted in effective cell inhibition in vitro and a remarkable synergistic anticancer effect in vivo. The cell apoptosis results indicated that OPTNs combined with HPTNs could induce HepG2 cell apoptosis and exert synergistic effects. In vivo pharmacodynamics analysis using a solid tumour-bearing mouse model indicated that OPTNs combined with HPTNs could suppress tumour growth by 67.61%.
  
  
  CONCLUSIONS
  This research suggests that the combined therapy system of OPTNs and HPTNs could be a new means of hepatoma therapy.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Fushun Central Hospital, Fushun 113006, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Bao
authors.affiliation: College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lv
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Deng
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Gao
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address: tiany2004@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles; D009828:Oleanolic Acid / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009828:Oleanolic Acid; D006493:Heparin; C014225:tocophersolan
keywords: Combination therapy; HepG2 cells; Heparin sodium; Liver cancer; Oleanolic acid; PLGA-TPGS nanoparticles