title: Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer.
abstract: OBJECTIVE
  The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC).
  
  
  METHODS
  In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo.
  
  
  RESULTS
  The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133+/CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P < 0.05).
  
  
  CONCLUSIONS
  The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy.
authors.affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education; Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yong-liang
authors.initials: YL
authors.lastname: Zhu
authors.forename: Fuming
authors.initials: F
authors.lastname: Qiu
authors.forename: Xian-guo
authors.initials: XG
authors.lastname: Wu
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Wang
authors.forename: Fu-qiang
authors.initials: FQ
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D018613:Microscopy, Confocal; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077150:Oxaliplatin; D018874:Spheroids, Cellular; D013229:Stearic Acids / Q000737:chemistry; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D013229:Stearic Acids; D000077150:Oxaliplatin; C031183:stearic acid; D048271:Chitosan