Nanodrug delivery systems for targeting the endogenous tumor microenvironment and simultaneously overcoming multidrug resistance properties

•The design of endogenous stimulus-responsive nanosystems (ESRNs) that can simultaneously combat MDR cancer is introduced.•The mechanisms of ESRNs to overcome MDR were summarized.•Drug release behavior and in vitro and in vivo anti-tumor efficacy in MDR cells or tumors of ESRNs are discussed.

Multidrug resistance (MDR) is a major obstacle to successful cancer therapy, especially for chemotherapy. Endogenous stimulus-responsive nanosystems (ESRNs), which were developed on the basis of the pathophysiological characteristics of the endogenous tumor microenvironment, have emerged as an efficient cancer therapy and have played an increasingly important role particularly in combating MDR cancers. These nanosystems can control the drug-releasing pattern temporally and spatially and can improve the accumulation of chemotherapeutic agents in MDR tumors or cells. This review focuses on recently published literature about nanosystems with endogenous stimulus-responsive features to overcome MDR, and it discusses their design and stimulus sensitivity, as well as their in vitro and in vivo anti-tumor efficacy in MDR tumors and cells.

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