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

Herein, we develop photodynamic therapy (PDT)-accelerated supramolecular nanomaterials based on α-cyclodextrin (α-CD), red-emitting AIEgens (namely, TPE-Py) and a 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, showing an increased fluorescence intensity. Interestingly, such a 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 coassembled into nanoparticles with the aid of DSPE-PEG2000 for anticancer investigation. Benefiting from the excellent PDT property and self-accelerated hypoxia-activated prodrug, these nanomaterials are successfully used for bioimaging and antitumor treatment in vitro and in vivo with good biosafety. This supramolecular strategy based on PDT and a hypoxia-responsive prodrug helps to enhance the precision of tumor treatment.