Multifunctional Self-Assembled Nanoplatform with AIEgen\nand Rapamycin-Mediated Tumor Microenvironment Remodeling via mTOR\nAxis to Enhance Photodynamic Therapy

Abstract

Photodynamic\ntherapy (PDT) is expected to become a new type of\nadjuvant therapy for cancer owing to its advantages, such as noninvasive,\nhigh spatiotemporal selectivity, and fewer side effects. However,\nconventional organic photosensitizers can easily aggregate in a biological\nsystem, leading to decreased fluorescence quenching and reactive oxygen\nspecies. Furthermore, attributed to the inherent hypoxia and immunosuppressive\nproperties of the complex tumor microenvironment (TME), the efficacy\nof PDT is severely restricted. Given this, groundbreaking work has\nconstructed carrier-free self-assembled nanoplatforms (TNTP-Ra NPs)\nbased on the newly synthesized zwitterionic PS-TNTP that has satisfactory\nimage-guided PDT and offers a new vision for delivery of rapamycin\nwith poor water solubility. Simultaneously, the coassembled rapamycin\nregulates the vigorous aerobic glycolysis of cancer cells and inhibits\nthe expression of PD-L1 by targeting the mTOR axis to remold hypoxia\nand immunosuppression TME. Accordingly, the multifunctional nanoplatform\nintegrating AIEgen-mediated PDT and TME remodeling is a forward-looking\nPDT design strategy.