Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review

Redox potential is regarded as a significant signal to distinguish between the extra-cellular and intra-cellular environments, as well as between tumor and normal tissues. Taking advantage of this physiological differentiation, various reduction-sensitive polymeric nanocarriers (RSPNs) have been designed and explored to demonstrate excellent stability during blood circulation but rapidly degrade and effectively trigger drug release in tumor cells. Therefore, this smart RSPN delivery system has attracted much attention in recent years, as it represents one of the most promising drug delivery strategies in cancer therapy. In this review, we will provide a comprehensive overview of RSPNs with various reducible linkages and functional groups up to date, including their design and synthetic strategies, preparation methods, drug release behavior, and their in vitro and in vivo efficacy in cancer therapy. In addition, dual- and triple-sensitive nanocarriers based on reducible disulfide bond-containing linkages will also be discussed.