AQ4N nanocomposites for hypoxia-associated tumor combination therapy

Hypoxia in solid tumors increases their invasiveness and resistance to therapy, presenting a formidable obstacle in tumor therapy. The hypoxia prodrug banoxantrone (AQ4N) undergoes conversion into its topoisomerase II inhibitor form AQ4 under hypoxic conditions, which inhibits tumor cells while leaving normal cells unharmed. Numerous studies have found that AQ4N significantly enhances the tumor effect while minimizing toxicity to normal tissues when combined with other drugs or therapeutic approaches. Thus, to maximize AQ4N's effectiveness, co-delivery of AQ4N with other therapeutic agents to the tumor site is paramount, leading to the development of multifunctional multicomponent AQ4N nanocomposites thereby emerging as promising candidates for combination therapy in tumor treatment. However, currently there is a lack of systematic analysis and reviews focusing on AQ4N. Herein, this review provides a comprehensive retrospect and analysis of the recent advancements in AQ4N nanocomposites. Specifically, we discuss the synergistic effects observed when AQ4N is combined with chemotherapeutic drugs, radiotherapy, phototherapy, starvation, sonodynamic therapy and immunotherapy in preclinical models. Moreover, the advantages, limitations, and future perspectives of different AQ4N nanocomposites are highlighted, providing researchers from diverse fields with novel insights into tumor treatment.