The Strategies of Integrating 4-Nitro-3-trifluoromethylaniline With Photosensitizers for Combined NO Gas and Photodynamic Therapy.

Nowadays, an increasing number of emerging therapeutic modalities are flourishing due to the high recurrence and intractability of cancer. Among them, NO gas therapy (NO GT) relies on NO donors that release NO radicals upon external or internal stimulation. Photodynamic therapy (PDT) is realized by the specific photosensitizers and light source. However, the clinical translation of NO is limited by its gaseous nature and the need for precise control over dosage and spatiotemporal distribution. Meanwhile, the efficacy of PDT is often compromised by tumor hypoxia. Consequently, the synergistic integration of PDT and NO GT has emerged as a cutting-edge paradigm in cancer treatment. Among the various NO donors, 4-nitro-3-trifuoromethylaniline (NTA) and its derivatives, as a prominent class of NO photodonors, have garnered sustained attention, which displayed various advantages such as high and controllable NO release ability and outstanding structural modification. In this review, we highlight the design of such bimodal therapeutic systems based on two methods of the combination of NTA and photosensitizers, namely, nanoassembly and molecular hybridization. By elucidating the design principles and synergistic antitumor effects of these two strategies, we summarize future development directions and remaining bottlenecks to provide rational guidelines for subsequent molecular design and biomedical research.