title: Emodin-Loaded PLGA-TPGS Nanoparticles Combined with Heparin Sodium-Loaded PLGA-TPGS Nanoparticles to Enhance Chemotherapeutic Efficacy Against Liver Cancer.
abstract: Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as a sustained and targeting delivery carrier and combined with emodin (EMO)-loaded PLGA-TPGS nanoparticles (EPTNs), which were investigated previously to form a combination therapy system for the treatment of liver cancer.
  
  
  
  To assess cellular uptake and evaluate the liver-targeting capacity by analyzing the drug concentrations and frozen slices, HS/eosin-loaded PLGA-TPGS nanoparticles, HS/fluorescein- loaded PLGA-TPGS nanoparticles and EMO/C6-loaded PLGA-TPGS nanoparticles, which contained eosin, fluorescein and C6 as fluorescent probes, respectively, were also prepared. All of these nanoparticles were characterized in terms of their size, size distribution, surface charge, drug loading, encapsulation efficiency, in vitro release profile and cellular uptake. The apoptosis of HepG2 cells induced by EPTNs in combination with HPTNs was determined by Annexin V-FITC staining and PI labelling.
  
  
  
  Transmission electron microscopy indicated that these nanoparticles were stably dispersed spheres with sizes ranging from 100 to 200 nm. The results demonstrated that fluorescent nanoparticles were internalized into HepG2 and HCa-F cells efficiently and had improved liver-targeting properties. The combination of EPTNs and HPTNs effectively inhibited cell growth in vitro and had a remarkable synergistic anticancer effect in vivo. EPTNs combined with HPTNs induced HepG2 cell apoptosis with synergistic effects. The liver H&E slice images of a hepatocarcinogenic mouse model indicated that EPTNs in combination with HPTNs significantly suppressed tumour growth in vivo.
  
  
  
  The research suggests that the combination therapy system of EPTNs and HPTNs could be a new direction for liver cancer therapy.
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Hongyan
authors: H
authors: Liu
authors: College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
authors: Hong
authors: H
authors: Xu
authors: College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
authors: Chenghong
authors: C
authors: Zhang
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Meng
authors: M
authors: Gao
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Xiaoguang
authors: X
authors: Gao
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Chuchu
authors: C
authors: Ma
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Li
authors: L
authors: Lv
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Dongyan
authors: D
authors: Gao
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Sa
authors: S
authors: Deng
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors: Changyuan
authors: C
authors: Wang
authors: College of Pharmacy, Dalian Medical University, Dalian, 116044, China. tiany2004@126.com.
authors: Yan
authors: Y
authors: Tian
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D065546:Drug Liberation; D004642:Emodin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000737:chemistry; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; C045866:peptide-Gly-Leu-amide; D014810:Vitamin E; D006493:Heparin; D004642:Emodin; C014225:tocophersolan
keywords: PLGA-TPGS nanoparticles; combination therapy; emodin; heparin sodium; liver cancer