title: Promoting antitumor activities of hydroxycamptothecin by encapsulation into acid-labile nanoparticles using electrospraying.
abstract: OBJECTIVE
  Acid-labile nanoparticles are proposed to enhance the tumor targeting and anti-tumor therapy of hydroxycamptothecin (HCPT) in response to the acidic microenvironment within cells and tumor tissues.
  
  
  METHODS
  HCPT was entrapped into matrix polymers containing acid-labile segments and galactose moieties (PGBELA) through an electrospraying technique. The antitumor activities of HCPT-loaded nanoparticles were evaluated both on HepG2 cells and after intravenous injection into H22 tumor-bearing mice.
  
  
  RESULTS
  The electrosprayed nanoparticles were obtained with enhanced loading efficiency and extended release of HCPT compared with other nanoparticle preparation methods. The acid-lability and targeting capability of PGBELA nanoparticles resulted in a 5 times higher inhibitory activity after incubation in pH 6.8 media compared to that of pH 7.4. Animal studies indicated that both the blood circulation time and tumor distribution of PGBELA nanoparticles were significantly increased. HCPT/PGBELA nanoparticles indicated a superior in vivo antitumor activity and fewer side effects than other treatments on the basis of tumor growth, animal survival rate, tissue necrosis and cell apoptosis evaluation.
  
  
  CONCLUSIONS
  Biodegradable PGBELA nanoparticles are capable of achieving site-specific drug delivery by active targeting and triggered release by acidic pH both in tumor tissues and after internalization within tumor cells, thereby providing a novel strategy for cancer treatment.
authors.affiliation: Key Laboratory of Advanced Technologies of Materials Ministry of Education of China School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, People's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Luo
authors.forename: Guoqing
authors.initials: G
authors.lastname: Jia
authors.forename: Haixing
authors.initials: H
authors.lastname: Song
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Liu
authors.forename: Guannan
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
mesh_terms: D000143:Acids / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002166:Camptothecin / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000143:Acids; D000970:Antineoplastic Agents; D004337:Drug Carriers; D002166:Camptothecin