Thermosensitive hydrogel as an injectable aggregation-induced emission photosensitizer delivery scaffold for lung cancer therapeutics with long-acting photodynamic therapy

Photodynamic therapy (PDT) has been increasingly utilized in the treatment of lung cancer due to its convenience and minimal invasiveness. However, the low therapeutic effect and bioavailability of photosensitizers pose significant challenges. Direct in-situ injection of photosensitizers often results in rapid loss from the tumor site and short retention times, necessitating multiple administrations during the treatment process, which can diminish the overall therapeutic efficiency for solid tumors. To address these limitations and enhance clinical outcomes, we developed an in-situ injectable thermosensitive hydrogel (P-TTPy) loaded with aggregation-induced emission (AIE) photosensitizer named TTPy for long-acting photodynamic therapy of lung cancer. In vitro experiments demonstrated the selective cytotoxicity of reactive oxygen species (ROS) generated by P-TTPy under white light excitation against lung cancer cells. The in vivo experiment involving subcutaneous lung cancer tumors in nude mice demonstrated that the in situ injection of thermosensitive hydrogel significantly extended the release duration of TTPy, resulting in superior growth inhibition of lung cancer tissue compared to the administration of TTPy alone. In summary, this strategy offered a new approach for enhancing photodynamic therapy for lung cancer.