title: Preparation of microspheres encapsulating a recombinant TIMP-1 adenovirus and their inhibition of proliferation of hepatocellular carcinoma cells.
abstract: OBJECTIVE
  The study aim was to prepare poly-DL-lactide-poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase-1 (TIMP-1) in an adenovirus to investigate its inhibition on the proliferation of hepatocellular carcinoma cells HepG2.
  
  
  METHODS
  Microspheres were prepared by encapsulating the recombinant TIMP-1 adenovirus into biodegradable PELA. The particle size, viral load, encapsulation efficiency and in-vitro release were measured. Microspheres were used to infect HepG2 cells, then infection efficiency was examined under a fluorescent microscope and ultrastructural changes assessed by TEM. Expression of TIMP-1 mRNA in HepG2 cells was examined by semi-quantitative RT-PCR and proliferation by MTT and cell growth curve assays.
  
  
  RESULTS
  We successfully prepared microspheres encapsulating recombinant TIMP-1 adenovirus with a diameter of 1.965μm, an encapsulation efficiency of 60.0%, a viral load of 10.5?108/mg and approximate 60% of virus release within 120 h, the total releasing time of which was longer than 240 h. The microspheres were confirmed to be non-toxic with blank microspheres. Infected HepG2 cells could stably maintain in-vitro expression of TIMP-1, with significantly effects on biological behaviour.
  
  
  CONCLUSIONS
  PELA microspheres encapsulating a recombinant TIMP-1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for polymer/chemistry-based gene therapy of hepatocellular carcinomas.
authors: Department of Gastrointestinal Surgery, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors: Dong
authors: D
authors: Xia
authors: Hui
authors: H
authors: Yao
authors: Qing
authors: Q
authors: Liu
authors: Liang
authors: L
authors: Xu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019562:Viral Load / Q000235:genetics
chemical_list: D011091:Polyesters; D011108:Polymers; D019715:Tissue Inhibitor of Metalloproteinase-1; C033616:poly(lactide)