Two-photon photodynamic therapy with curcumin nanocomposite

Two-photon photodynamic therapy (TP-PDT) offers an innovative approach to cancer treatment that utilizes near-infrared light to activate photosensitizers and generate reactive oxygen species (ROS) for targeted cancer cell elimination. TiO2-CUR-Sofast (TCS), which uses TiO2 nanoparticles and Sofast cationic polymer to modify curcumin (CUR), has demonstrated potential as a photosensitizer under visible light irradiation, addressing the limitations of CUR's narrow spectral range and low bioavailability. This study explores the utility of the two-photon technique to activate TCS within the infrared spectrum, aiming to enhance ROS production and penetration depth compared to traditional CUR. TCS exhibits a significantly higher ROS production at 900 nm excitation wavelength, approximately 6–7 times that of CUR, signifying a substantial increase in efficiency. In TP-PDT, TCS showed significant phototoxicity against HeLa and T24 cell lines compared to CUR. Furthermore, TCS's photodynamic efficacy is further confirmed by cell apoptosis and necrosis studies, where approximately 89 % of cells treated with TCS under 900 nm light irradiation were observed in an apoptosis/necrosis state. And the TP-PDT effect in deep tissue was simulated using pig skin. It shows that the two-photon excitation has a significant penetration depth advantage over the single-photon excitation. These results indicate that the two-photon PDT scheme of TCS has greater potential than the single-photon PDT scheme in the treatment of cancer, and provides an experimental foundation for the effective treatment of deep lesions. •TiO2-CUR-Sofast (TCS) demonstrates enhanced photodynamic activity via two-photon activation.•TCS exhibits increased ROS generation at 900 nm excitation, outperforming conventional by a factor of 6–7.•TCS shows pronounced phototoxicity against HeLa and T24 cancer cell lines in two-photon photodynamic therapy (TP-PDT).•TCS's TP-PDT efficacy is confirmed with deep tissue penetration advantage in a pig skin model.•The TP-PDT with TCS provides a foundation for effective deep lesion therapy.