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Abstract
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.