Self-guiding Polymeric Prodrug Micelles with Two AIE Photosensitizers for Enhanced Chemo-Photodynamic Therapy
Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N3) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L1, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L2, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both in vivo and in vitro studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.