ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage.
Targeting tumor cells is an important strategy to improve the selectivity of cancer therapies. With the advanced studies in cancer biology, we know that cancer cells are usually under increased oxidative stress. The high level of reactive oxygen species in cancer cells has been exploited for developing novel therapeutic strategies to preferentially kill cancer cells. Our group, amongst others, have used boronic acids/esters as triggers for developing ROS-activated anticancer prodrugs that target cancer cells. The selectivity was achieved by combining a specific reaction between boronates and H2O2, with the efficient masking of drug toxicity in the prodrug via boronates. Prodrugs activated via ferrocene-mediated oxidation have also been developed to improve the selectivity of anticancer drugs. We describe how the strategies of ROS-activation can be used for further development of new ROS-targeting prodrugs, eventually leading to novel approaches and/or combined technology for more efficient and selective treatment of cancers.
Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer St., Milwaukee, WI 53211, USA. pengx@uwm.edu
Xiaohua
X
Peng
Varsha
V
Gandhi
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001896:Boron Compounds / Q000494:pharmacology; D015195:Drug Design; D005296:Ferrous Compounds / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000075163:Metallocenes; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D001896:Boron Compounds; D005296:Ferrous Compounds; D000075163:Metallocenes; D011355:Prodrugs; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C004998:ferrocene