Water-dispersible fullerene aggregates as a targeted anticancer prodrug with both chemo- and photodynamic therapeutic actions.

Abstract

Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer prodrug system based on water-dispersible fullerene (C60) aggregates is introduced; this prodrug system demonstrates active targeting, pH-responsive chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto fullerene while maintaining an overall size of approximately 135 nm produces a more specific anticancer prodrug. This prodrug can enter folate receptor (FR)-positive cancer cells and kill the cells via intracellular release of the active drug form. Moreover, the fullerene aggregate carrier exhibits PDT action; the cytotoxicity of the system towards FR-positive cancer cells is increased in response to light irradiation. As the DOX drug molecules are conjugated onto fullerene, the DOX fluorescence is significantly quenched by the strong electron-accepting capability of fullerene. The fluorescence restores upon release from fullerene, so this fluorescence quenching-restoring feature can be used to track intracellular DOX release. The combined effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX-fullerene aggregate prodrug. This study provides useful insights into designing and improving the applicability of fullerene for other targeted cancer prodrug systems.

• Authors: Jianquan Fan, Gang Fang, Fang Zeng, Xiaodan Wang, Shuizhu Wu
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 9 Issue 4 Pg. 613-21 (Feb 25 2013) ISSN: 1613-6829 [Electronic] Germany
• PMID: 23117954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Fullerenes
• Prodrugs
• Water

Topics

• Antineoplastic Agents (chemistry, therapeutic use)
• Cell Line, Tumor
• Fullerenes (chemistry)
• HeLa Cells
• Humans
• Photochemotherapy
• Prodrugs (chemistry)
• Water (chemistry)