Nanomaterials for Tumor Hypoxia Relief to Improve the Efficacy of ROS-Generated Cancer Therapy

Abstract

Given the fact that excessive levels of reactive oxygen species (ROS) induce damage to proteins, lipids, and DNA, various ROS-generating agents and strategies have been explored to induce cell death and tumor destruction by generating ROS above toxic threshold. Unfortunately, hypoxia in tumor microenvironment (TME) not only promotes tumor metastasis but also enhances tumor resistance to the ROS-generated cancer therapies, thus leading to ineffective therapeutic outcomes. A variety of nanotechnology-based approaches that generate or release O2 continuously to overcome hypoxia in TME have showed promising results to improve the efficacy of ROS-generated cancer therapy. In this minireview, we present an overview of current nanomaterial-based strategies for advanced cancer therapy by modulating the hypoxia in the TME and promoting ROS generation. Particular emphasis is put on the O2 supply capability and mechanism of these nanoplatforms. Future challenges and opportunities of design consideration are also discussed. We believe that this review may provide some useful inspiration for the design and construction of other advanced nanomaterials with O2 supply ability for overcoming the tumor hypoxia-associated resistance of ROS-mediated cancer therapy and thus promoting ROS-generated cancer therapeutics.

Tumor microenvironment‐regulating nanomedicine design to fight multi‐drug resistant tumors

“…Therefore, hypoxia, a unique characteristic of solid tumors, has been proven to be a promising target in the design of antitumor systems (Zhao et al, 2020). An increasing number of researchers have been devoted to developing approaches to overcome or take advantage of hypoxia to reverse hypoxia-related drug resistance (Ruan et al, 2021).…”

Engineering defected 2D Pd/H-TiO2 nanosonosensitizers for hypoxia alleviation and enhanced sono-chemodynamic cancer nanotherapy

“…It should be recognized that hypoxia, the prevalent hallmark of the overwhelming majority of solid tumors induced by rapid proliferation and aberrant neovasculature, is a bottleneck for cancer treatment [ 26 – 28 ]. Definitely, the low oxygen tension not only contributes to tumor aggressiveness and metastasis but also results in compromised cytotoxic effect [ 29 , 30 ]. On the one hand, as the donor of singlet oxygen ( 1 O 2 ), insufficient oxygen supply will inevitably impact the harvest of ROS and impair the potency of SDT [ 31 ].…”

“…Therefore, it is sensible to replenish oxygen to relieve hypoxia and synchronously enhance SDT and CDT. Notably, the higher level of H 2 O 2 in the tumor region can be decomposed into oxygen in the presence of the catalase accordingly can serve as feasible origination of oxygen to remit hypoxia [ 30 , 33 , 34 ]. And fortunately, diverse nanozymes that mimic natural enzyme capabilities have been extensively investigated and validated to be prospective alternatives to the scant autologous catalase in the tumor location [ 35 , 36 ].…”

Engineered Nanostructured Photocatalysts for Cancer Therapy

“…The aberrant growth of tumors provokes an irregular creation of blood vessels causing limited O 2 supply [24]. Thus, the in-situ generation of O 2 is considered a major advantage for a photocatalyst because of the continuous photogeneration of ROS in a hypoxic environment [25]. Regarding GSH, its key role as the main antioxidant molecule in animal cells is responsible for ROS counterbalance in diverse metabolic routes [26].…”