Strategies based on metal-based nanoparticles for hypoxic-tumor radiotherapy
Radiotherapy (RT) is one of the most effective and frequent clinical cancer treatments. Nevertheless, RT can cause damage to normal tissues around tumor under high-dose ionizing radiation. Sparked by the versatile metal-based nanomaterials, great efforts have been devoted to develop the nanomaterials with high-Z metal elements as radiosensitizers by depositing more energy into tumor for RT enhancement. However, these metal-based nanomaterials-mediated RT are highly O2-dependent. Unfortunately, the O2 concentrations within the majority of solid tumors exhibit low levels, which seriously hampers the antitumor efficacy of these nanomaterials during RT. Therefore, the development of novel metal-based nanomaterials as radiosensitizers capable of avoiding the radioresistance induced by the tumor hypoxia are highly desirable and important. Currently, the most effective approaches to reverse radioresistance of hypoxic tumor are to introduce nanomaterials with the O2-elevated ability by delivering exogenous O2, generating O2 in situ, increasing intratumoral blood flow, or reducing HIF-1 expression to harness O2 level in solid tumors. Besides that, recently, some innovative and simple strategies by employing nanoradiosensitizers with diminished oxygen dependence also have been applied to combat the unmet hypoxic challenges, in which nanoradiosensitizers can target tumor hypoxia for selective RT, enhance oxygen-independent ROS generation, or combine with non-oxygen dependent cancer therapy for synergistic treatments. These approaches and strategies provide new avenues for enhanced hypoxic-tumor RT. Nevertheless, the overall review aimed specifically at these strategies is still rare. Herein, we present an overview about the recent advances of metal-based nanomaterials for hypoxic-tumor RT, and give a detailed discussion about the design and working mechanisms of these strategies in their application of RT. Finally, the current challenges and future perspectives are also pointed out in this field.