Improving cancer therapy through the nanomaterials-assisted alleviation of hypoxia

Hypoxia, resulting from the imbalance between oxygen supply and consumption is a critical component of the tumor microenvironment. It has a paramount impact on cancer growth, metastasis and has long been known as a major obstacle for cancer therapy. However, none of the clinically approved anticancer therapeutics currently available for human use directly tackles this problem. Previous clinical trials of targeting tumor hypoxia with bioreductive prodrugs have failed to demonstrate satisfactory results. Therefore, new ideas are needed to overcome the hypoxia barrier. The method of modulating hypoxia to improve the therapeutic activity is of great interest but remains a considerable challenge. One of the emerging concepts is to supply or generate oxygen at the tumor site to increase the partial oxygen pressure and thereby reverse the hypoxia and its effects. In this review, we present an overview of the recent progress in the development of novel nanomaterials for the alleviation of hypoxic microenvironment. Two main strategies for hypoxia augmentation, i) direct delivery of O₂ into the tumor, and ii) in situ O₂ generations in the tumor microenvironment through different methods such as catalytic decomposition of endogenous hydrogen peroxide (H₂O₂) and light-triggered water splitting are discussed in detail. At present, these emerging nanomaterials are in their early phase and expected to grow rapidly in the coming years. Despite the promising start, there are several challenges needed to overcome for successful clinical translation.