Recent progress of chemodynamic therapy-induced combination cancer therapy

Chemodynamic therapy (CDT) is an emerging cancer treatment strategy that uses CDT agents to convert hydrogen peroxide (H2O2) into the hydroxyl radical (OH), the most harmful reactive oxygen species (ROS) by the Fenton/Fenton-like reactions, thus inducing cell apoptosis and necrosis. This treatment method has been widely studied because of its minimal invasiveness and high tumor specificity, and has become a popular topic of research. Despite the great potential of CDT in tumor treatment, the clinical conversion of CDT is still facing challenges: 1) the relatively high pH of the tumor sites is not suitable for the occurrence of most Fenton/Fenton-like reactions; 2) the low concentration of endogenous H2O2 at the tumors is not enough to generate continuous ROS such as OH; and 3) the high expression of reducing substances (e.g., glutathione, GSH) in the tumor microenvironment (TME) weakens the therapeutic effect of CDT. These limitations make it difficult for CDT alone to completely eliminate malignant tumors. Therefore, CDT-based combined treatment strategies have been widely developed. CDT-based combined therapy refers to the combination of CDT and other cancer treatments (e.g., photo-induced therapy, chemotherapy, sonodynamic therapy, starvation therapy, and gas therapy), which can produce a synergistic anticancer effect. This combined therapy can reduce individual drug-related toxicity and significantly enhance therapeutic efficiency, which has recently seen rapid development. This review begins by defining CDT, then it identifies the problems faced in CDT and proposes various strategies to enhance CDT performance, primarily focusing on CDT-based combined cancer treatment. The problems, opportunities, and challenges of CDT-based combination cancer therapy are also summarized, thereby providing a reference for the future development of CDT-based combined therapy.