Biodegradable polymer-platinum drug conjugates to overcome platinum drug resistance

摘要

Drug resistance and severe dose-dependent side effects are the major obstacles to the further use of platinum agents. Two well-acknowledged mechanisms of resistance are the decreased intracellular accumulation and the increased sulfur-binding-detoxification of platinum agents. The polymer-drug conjugate approach can remarkably enhance the uptake of substances by cancer cells, therefore can achieve better anticancer effects with lower dosage, and thus reduce the dose-dependent side effects. Here we synthesized a biodegradable polymer containing pendant 1,2-bidentate carboxyl groups to chelate platinum without introducing sulfur atoms to potentially detoxify the platinum drugs. The polymer-platinum conjugate formed nanomicelles showed significantly increased intracellular accumulation and could partially overcome drug resistance in ovarian cancer cells.