Hypoxia-responsive nanoparticles for tumor-targeted drug delivery

Hypoxia is a negative prognostic indicator of solid tumors. Increasing evidence indicates that the intratumoral hypoxic microenvironment is strongly related to enhanced tumor aggressiveness, decreased therapeutic effect and poor prognosis of chemotherapy, radiotherapy (RT), and photodynamic therapy (PDT). However, due to an unusual gene expression profile and abnormal metabolism, enzymes responsible for reduction reactions or electron donation are highly reactive in hypoxic tumor cells and provide the possibility of exploiting targeted drug delivery systems for cancer therapy. Taking advantage of the specific bioreductive microenvironments in hypoxic tumors, researchers have recently developed several hypoxia-responsive nanoparticles (HR-NPs) for targeted cancer therapy. In this review, the hypoxia-responsive molecular structures that were employed to construct HR-NPs are presented. Furthermore, the strategies to make use of these HR-NPs, and the recent advances in HR-NPs for efficient tumor-targeted drug delivery and cancer therapy are highlighted.