Enhancing biosafety in photodynamic therapy: progress and perspectives

Photodynamic therapy (PDT), a non-invasive method with minimal drug-resistance, high spatiotemporal selectivity, and involvement of reactive oxygen species (ROS) in phototherapy methods, plays an increasingly vital role in cancer treatment. Throughout the development of PDT, enhancing the therapeutic efficacy of photosensitizers (PSs) has been a consistent research focus. However, the continuous progress and widespread use of PDT have highlighted the importance of its safety. For instance, the significant side effects of PSs remain a notable issue, given that traditional PSs utilize an "always-ON" strategy, leading to severe phototoxic symptoms such as burning sensations, skin redness, and scabbing. Furthermore, patients must avoid natural light exposure for several weeks post-treatment. Additionally, attention should be directed towards the metabolism and clearance pathway, a critical pharmacokinetic feature that eliminates unwanted materials from the body post-treatment to prevent toxicity and damage. This review summarizes recent developments in smart PSs that exhibit highly effective cancer therapeutic functions with enhanced biosafety, addressing the inconveniences faced by patients following conventional PDT. In addition, the review discusses the challenges and future prospects for promoting the increasing application of PDT in clinical practice.