Photosensitizers with multiple degradation modes for efficient and postoperatively safe photodynamic therapy

Photodynamic therapy (PDT) is emerging as a powerful tool for cancer treatment due to its unique advantages in terms of noninvasive and spatiotemporal selectivity. However, the residue of photosensitizers (PSs), which usually lead to thorny post-treatment side effects after photodynamic therapy (PDT), is one of bottlenecks for clinical translation. Herein, PSs with multiple degradation modes are developed to solve this issue. Upon 660 nm laser excitation, PSs can produce different types of reactive oxygen species (ROS), in which O-1(2) and O-2(center dot-) could kill the cancer cells, while center dot OH could oxide the PSs themselves for photodegradation. After PDT, the residual few number of PSs could be further oxidized by endogenous ROS for biodegradation, and the degradation products could be further excreted by urine. This process therefore solves the slow-metabolism issue of traditional PSs. Among them, SQSe demonstrates the highest killing efficiency with best degradation ability, as confirmed by both in vitro and in vivo results. The postoperative safety of SQSe is further verified by assessment on in vivo artificially induced post-operative side effects.

Automated summary

Photodynamic therapy (PDT) is a powerful cancer treatment tool due to its noninvasive and spatiotemporal selectivity. Residue of photosensitizers (PSs) after PDT causes post-treatment side effects, which has hindered clinical translation. To solve this issue, PSs with multiple degradation modes are developed. These PSs can produce different reactive oxygen species (ROS) upon laser excitation, and the residual PSs can be further oxidized for biodegradation and excretion. SQSe shows the highest killing efficiency and degradation ability, as confirmed by in vitro and in vivo results. Its postoperative safety is also verified.