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  • Dual role of photosensitizer and carrier material of fullerene in micelles for chemo-photodynamic therapy of cancer.

Dual role of photosensitizer and carrier material of fullerene in micelles for chemo-photodynamic therapy of cancer.

Journal of pharmaceutical sciences (2014-09-02)
Xinhong Guo, Rui Ding, Ying Zhang, Ling Ye, Xin Liu, Caiping Chen, Zhenzhong Zhang, Yun Zhang
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.

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