Engineering principles of nanomedicine in gas-mediated enhanced anti-tumor photodynamic therapy.

Photodynamic therapy (PDT), a highly selective treatment with low drug resistance and invasiveness, has brought new hope in tumor treatment but is severely compromised by the distribution of photosensitizers in the immunosuppressive tumor microenvironment. Inspired by the synergetic function of gas and PDT, gas therapy improves the intratumoral distribution of photosensitizers and modulates the immune response, thereby raising a promising scope for addressing the current bottlenecks of PDT. In this review, we summarize the tumor-suppression pathways of different gases, with emphasis on the cascading effects of reactive oxygen species (ROS) and gases. Furthermore, we elaborate on the design principles of spatiotemporally controlled gas delivery systems. Finally, we summarize the challenges in gas-assisted PDT and issues that require further research.