Polymeric Encapsulation of a Ru(II)-Based Photosensitizer for Folate-Targeted Photodynamic Therapy of Drug Resistant Cancers

The currently used photodynamic therapy (PDT) photosensitizers (PSs) are generally associated with a poor cancer cell selectivity, which is responsible for some undesirable side effects. To overcome these problems, there is an urgent need for a selective drug delivery system for PDT PSs. Herein, the encapsulation of a promising Ru(II) polypyridine complex in a polymer with terminal folate groups to form nanoparticles is presented. While the Ru(II) complex itself has a cytotoxic effect in the dark, the encapsulation is able to overcome this drawback. Upon light exposure, the nanoparticles were found to be highly phototoxic in 2D monolayer cells as well as 3D multicellular tumor spheroids upon 480 or 595 nm irradiation. Importantly, the nanoparticles demonstrated a high selectivity for cancerous cells over noncancerous cells and were found to be active in drug resistant cancer cells lines, indicating that they are able to overcome drug resistances.

Automated summary

This study presents a method to encapsulate a promising Ru(II) polypyridine complex in polymer nanoparticles, improving the selectivity and efficacy of photodynamic therapy. The nanoparticles exhibit high phototoxicity towards cancer cells and are effective in drug resistant cancer cells, indicating their potential to overcome drug resistance.