title: Enhanced antitumor efficacy of gemcitabine-loaded temperature-sensitive liposome by hyperthermia in tumor-bearing mice.
abstract: BACKGROUND
  Gemcitabine-loaded TSL (Gem-TSL) was used in combination with hyperthermia (HT) to treat the colon adenocarcinoma-bearing BALB/c mice for improved anticancer effect following intravenous administration.
  
  
  METHODS
  A new temperature-sensitive liposome (TSL), composed of DPPC:DMPC:DSPC (4:1:1 molar ratio) releasing the encapsulated gemcitabine (Gem) at 41 °C, was developed and evaluated for enhanced antitumor efficacy both in vitro and in vivo.
  
  
  RESULTS
  Drug release from the TSL was sharply increased at 41 °C and in vitro cytotoxicity of Gem-TSL in colon adenocarcinoma cells (CT-26) was 10 times higher than the free drug (IC50 = 0.3 μM versus 3 μM). Apoptosis seemed to be the main mechanism of cell death as the treatment of the cells with Gem-TSL increased the caspse-3/7 activity by 1.5-fold and also caused the fragmentation of chromatin DNA. Gem-TSL suppressed the tumor growth in CT-26-bearing BALB/c mice more stronger than the free gemcitabine after intravenous administration. Moreover, this in vivo antitumor efficacy of Gem-TSL was further increased when HT was added.
  
  
  CONCLUSIONS
  This study suggests that this new TSL-Gem formulation could serve as a new chemotherapy modality together with HT.
authors.affiliation: Research Center for Cell Fate Control (RCCFC), College of Pharmacy, Sookmyung Women's University , Seoul , South Korea.
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lim
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Shin
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Choi
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D053938:DNA Fragmentation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006979:Hyperthermia, Induced / Q000379:methods*; D020128:Inhibitory Concentration 50; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D013696:Temperature; D000093542:Gemcitabine
chemical_list: D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D008081:Liposomes; D003841:Deoxycytidine; D053148:Caspase 3; D053179:Caspase 7; D000093542:Gemcitabine