title: Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells.
abstract: METHODS
  Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles.
  
  
  RESULTS
  The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44(+)/CD24(+) cells (putative colorectal cancer stem cell markers) both in vitro and in vivo.
  
  
  CONCLUSIONS
  The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.
authors.affiliation: Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Chen
authors.forename: Chao
authors.initials: C
authors.lastname: Ni
authors.forename: Junshu
authors.initials: J
authors.lastname: Zhang
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D001835:Body Weight / Q000187:drug effects; D051927:CD24 Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004355:Drug Stability; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010316:Particle Size; D011897:Random Allocation; D012995:Solubility; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051927:CD24 Antigen; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D008823:Micelles; D048271:Chitosan; D003474:Curcumin