Research progress on tumor hypoxia-associative nanomedicine

Hypoxia at the solid tumor site is generally related to the unrestricted proliferation and metabolism of cancerous cells, which can cause tumor metastasis and aggravate tumor progression. Besides, hypoxia plays a substantial role in tumor treatment, and it is one of the main reasons that malignant tumors are difficult to cure and have a poor prognosis. On account of the tumor specific hypoxic environment, many hypoxia-associative nanomedicine have been proposed for tumor treatment. Considering the enhanced targeting effect, designing hypoxia-associative nanomedicine can not only minimize the adverse effects of drugs on normal tissues, but also achieve targeted therapy at the lesion site. Mostly, there can be three strategies for the treatment of hypoxic tumor, including improvement of hypoxic environment, hypoxia responsive drug release and hypoxia activated prodrug. The review describes the design principle and applications of tumor hypoxia-associative nanomedicine in recent years, and also explores its development trends in solid tumor treatment. Moreover, this review presents the current limitations of tumor hypoxia-associative nanomedicine in chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy, which may provide a reference for clinic translation of tumor hypoxia-associative nanomedicine.