Enriched photosensitizer for deep-seated-tumor photodynamic therapy

Photodynamic therapy (PDT) is an innovative approach that utilizes photochemical reactions for non-invasive disease treatment. Conventional PDT is limited by the low penetration depth of visible light required for activation. Herein, we employed upconversion nanoparticles (UCNPs) to extend the activation wavelength of photosensitizers into the infrared range, enabling a treatment depth of over 10 mm. Furthermore, we also used the abundant amino groups of branched polyethyleneimine (PEI) with spatial structure to enhance the loading capacity of protoporphyrin (PPIX), and we ultimately improved skin tumor clearance rates. Moreover, we achieved tumor-specific treatment by utilizing folic acid (FA) targeting and active enrichment of PPIX. According to cellular experimental results, we demonstrated the remarkable reactive oxygen species generation capability of the material and ultra-low dark toxicity. Additionally, we investigated the apoptosis mechanism and demonstrated that the synthesized nanoparticle stimulates the up-regulation of apoptosis-associated proteins Bax/Bcl-2 and Cyto c. During in vivo experiments involving intravenous injection in mouse tails, we investigated the anticancer efficacy of the nanoparticle, confirming its excellent PDT effects. This research provides a promising avenue for future non-invasive treatment of deep-seated tumors, offering a method for the treatment and management of specific cancers.