NIR light-triggered peroxynitrite anion production via direct lanthanide-triplet photosensitization for enhanced photodynamic therapy

Peroxynitrite anion (ONOO−), a product derived from reaction between reactive oxygen species (ROS) and nitric oxide (NO), is considered to be a more toxic reactive species than most ROS for cancer photodynamic therapy (PDT). To promote the PDT effect, a viable method is to develop rational strategies for efficient ONOO− generation at targeted tumor sites. Herein, a heterostructure nanocomposite containing ZnO-coated lanthanide nanoparticles (LnNPs) is reported for ONOO−-based PDT. In this nanocomposite, Nd3+-doped LnNPs are employed to realize efficient NIR-light-triggered ROS generation by activating the triplet state of chlorin-e6 (Ce6) photosensitizers via a direct lanthanide-to-triplet sensitization mechanism. Meanwhile, ZnO in the composite catalyzes the decomposition of S-nitrosoglutathione (GSNO) to generate NO in the tumor microenvironment. The coupled system allows the combination of photo-induced ROS and NO to produce ONOO−, leading to drastically promoted cancer cell apoptosis and tumor growth inhibition. This study establishes a new apoptosis-inducing PDT agent, which is potentially active in drug resistant malignancies.