Photodynamic Therapy-Accelerated Hypoxia-Responsive Prodrug Release for Synergistic Photo-Chemotherapy of Melanoma Cancer based on Noncovalent Interactions

Chemotherapy plays a crucial role in clinical cancer treatment. However, it is confronted with dire challenges in achieving high specificity due to their indiscriminate interaction with both tumor cells and normal cells. Herein, we develop a photodynamic therapy (PDT)-accelerated supramolecular nanomaterials based on α-cyclodextrin (α-CD), red-emitting AIEgens (namely TPE-Py) and hypoxia-activated paclitaxel-based prodrug (namely PTX-NB), which surpasses hypoxia limitations and enhances the efficiency of chemotherapeutic prodrug release in melanoma. The cationic AIEgen functions as a guest molecule, capable of forming a supramolecular complex with α-CD in a 1:1 binding ratio. Notably, the as-prepared TPE-Py⊂α–CD complex shows an increased fluorescence intensity thanks to restriction of free motion of AIEgens. Interestingly, such complex accelerates type II ROS generation through consumption of intracellular oxygen to result in a severe hypoxic microenvironment to facilitate hypoxia-responsive prodrug release. Then, TPE-Py⊂α–CD and PTX-NB are co-assembled into nanoparticles with the aid of DSPE-PEG2000 for anticancer investigation. Benefitting from the excellent PDT property and self-accelerated hypoxia-activated prodrug, this supramolecular nanomaterial is successfully used for bioimaging and antitumor treatment in vitro and in vivo with good biosafety. This supramolecular synergistic strategy based on PDT and hypoxia-responsive prodrug help to enhance the precision of tumor treatment.