Tailoring polymeric nanocarriers for hypoxia-specific drug release: Insights into design and applications in clinics

초록

Hypoxic environment-responsive nanocarriers represent a promising future in targeted drug delivery to solid tumors since hypoxia has an important role in tumor proliferation, angiogenesis, and metastasis, offering a means to overcome resistance to cancer therapy. Exploiting hypoxic conditions for cancer treatment can be achieved through two distinct approaches. Firstly, by using hypoxia-activated prodrugs (HAP) and secondly by developing nanocarriers in response to hypoxia. HAPs, such as tirapazamine, metronidazole, etc can convert into anti-cancer drugs upon hypoxic conditions, reducing the chances of side effects by eliminating non-specific targeting due to the low oxygen content and the presence of numerous bioreductive enzymes like azo, nitroreductase. However, HAPs were unsuccessful in clinical trials due to low extravascular transport which implies the necessity of nanocarriers for their effective delivery to tumor site. Thus, precise designing of the hypoxia-responsive nanocarriers that can deliver anticancer agents or HAPs is of utmost importance for tumorspecific delivery. The current review focuses on various nano vehicles, including liposomes, micelles, hydrogel, nanogel, and dendrimers synthesized by polymeric materials to render them hypoxia-responsive properties. Here, we explain the release of chemotherapeutic drugs from the nanocarriers in the tumor cells, due to the reduction of the hypoxia-responsive functional groups. Furthermore, the limitations and potential considerations of improving hypoxia-responsive drug administration are discussed.

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