title: Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma.
abstract: BACKGROUND
  Cytotoxic drugs are non-selective between normal and pathological tissue, and this poses a challenge regarding the strategy for treatment of tumors. To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. We investigated the ability of oxaliplatin long-circulating liposomes (PEG-liposomal L-oHP) to provide an improved therapeutic index of colorectal carcinoma.
  
  
  RESULTS
  We determined that PEG- liposomes conjugated with cells at 2 h, with a mean fluorescence intensity that was enhanced upon extended induction time. The PEG-liposomal L-oHP induced a significant apoptotic response as compared with free L-oHP, 23.21% ± 3.38% vs. 16.85% ± 0.98%, respectively. Fluorescence imaging with In-Vivo Imaging demonstrated that PEG- liposomes specifically targeted tumour tissue. After intravenous injections of PEG-liposomal L-oHP or free L-oHP, the tumour volume suppression ratio was 26.08% ± 12.43% and 18.19% ± 7.09%, respectively, the percentage increased life span (ILS%) was 45.36% and 76.19%, respectively, and Bcl-2, Bax mRNA and protein expression in tumour tissue was 0.27-fold vs. 0.88-fold and 1.32-fold vs. 1.61-fold compared with free L-oHP, respectively.
  
  
  CONCLUSIONS
  The PEG-liposomal L-oHP exhibited a tendency to target tumour tissue and demonstrated a significantly greater impact on apoptosis compared to free oxaliplatin.
authors.affiliation: Department of Gastrointestinal Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, Chongqing, China. fzx990521@sina.com
authors.forename: Chuang
authors.initials: C
authors.lastname: Yang
authors.forename: Hai Z
authors.initials: HZ
authors.lastname: Liu
authors.forename: Zhong X
authors.initials: ZX
authors.lastname: Fu
authors.forename: Wei D
authors.initials: WD
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000077150:Oxaliplatin; C052617:Bcl2 protein, mouse