title: Dual role of photosensitizer and carrier material of fullerene in micelles for chemo-photodynamic therapy of cancer.
abstract: Derivatives of fullerene (C60) as photosensitizers have rarely been studied as delivery carrier materials. The focus of this study was to explore the potential advantages of diadduct malonic acid-fullerene (DMA-C60) as delivery carrier materials and combination of chemo-phototherapy of some tumors. In this study, DMA-C60 and docetaxel (DTX) were coentrapped in micelles (MCs) (DMA-C60/DTX-MC). The addition of DMA-C60 could obviously improve static stability and decrease critical MC concentration of DTX-MC without hemolysis. The sustained release of DTX and DMA-C60 could be achieved, following Higuichi and first-order model, respectively. DMA-C60 could still produce reactive oxygen species efficiently in HeLa cells after encapsulation in MC. The addition of DMA-C60 under irradiation caused DTX-MC more stronger cytotoxicity, cell cycle changes, and more early apoptotic cells in vitro. More importantly, after intravenous injection, the addition of DMA-C60 in DTX-MC could result in 2.25-fold and 4.57-fold longer mean residence time compared with DTX-MC and Duopafei(®) , increase drug intratumoral distribution and decrease drug distribution in heart and kidney, and enhance antitumor effect under irradiation without body weight loss. These results suggested tremendous promise of DMA-C60 as carrier materials of MC and significant advantages in combination of chemo-phototherapy of some tumors. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3225-3234, 2014.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Caiping
authors.initials: C
authors.lastname: Chen
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis; D002453:Cell Cycle; D037741:Fullerenes / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D037741:Fullerenes; D008823:Micelles; D017319:Photosensitizing Agents
keywords: antitumor effect; cancer chemotherapy; cellular mechanisms; controlled release/delivery; diadduct malonic acid-fullerene; excipients; micelles; pharmacokinetics; photosensitive