Photodynamic therapy is based on the effective excitation of a photosensitizer at the appropriate time after its administration (drug-to-light-interval, DLI) to produce ROS.1 Our research interests have focused on the photochemical properties of nanoformulated photosensitizers from the groups of bacteriochlorins2 and phthalocyanines3 and their application either in vascular targeted PDT (V-PDT, DLI=15 min) or cellular targeted PDT (C-PDT, DLI=24h or 72 h).
Our newly synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO2tBu demonstrated an outstanding ability to generate singlet oxygen (Φ△ = 0.87-0.99), while ZnSO2tBu in addition to 1O2 (Φ△ = 0.45-0.48) generated efficiently other reactive oxygen species, in particular ·OH. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using triblock copolymers to improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake when the phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Vascular-targeted photodynamic therapy (V-PDT), led to complete tumor eradication in 84% for ZnSO2tBu and 100% for PtSO2tBu treated mice, and no recurrence has so far been observed for up to two months after treatment. In the case of PtSO2tBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.
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Acknowledgment
This research was funded by the National Science Center (NCN) within the framework of the Opus project no 2020/37/B/NZ7/04157 given to J.M.D.