Targeting hypoxic and acidic tumor microenvironment by nanoparticles: A review

Hypoxia is a usual property of solid tumors that is characterized by low oxygen and nutrition levels. It is also a good marker for aggressive tumor expansion, metastasis, and poor patient prognosis. Hypoxia amplifies the abnormal metabolism of tumors and the generation of lactate, leading to the accumulation of lactic acid in the tumor microenvironment (TME). Both hypoxia and tumor acidity can cause immune repression in TME, which in turn facilitates tumor invasion and therapy resistance. Therefore, targeting hypoxia and an acidic environment in TME has attracted interest in targeted delivery of antitumor drugs. Nanoparticles have achieved remarkable attention as potential carriers for targeted drug delivery to hypoxic tumor regions. These nanoscale particles possess unique capacities that enable them to conquer biological barriers and precisely accumulate and liberate antitumor drugs in hypoxic and acidic areas. Specific nanoparticles such as pH-sensitive or functionalized nanoparticles for targeting hypoxic makers can precisely deliver antitumor agents into TME. Additionally, oxygen-carrying nanoparticles can be suggested to reduce hypoxia and subsequent altered metabolism in the tumor. Remodeling the hypoxic and acidic environment of the tumor can boost anticancer immunity, prevent the inactivation of chemotherapy drugs, and also amplify the radiosensitization of hypoxic cells in the tumor. In the current review, we provide an outline of the current strategies employed to target the hypoxic and acidic TME using nanoparticles. Furthermore, the findings of clinical investigations and also future directions for utilizing pH-sensitive and hypoxia-targeting nanoparticles will be overviewed.