Multifunctional Self-Assembled Nanoplatform with AIEgen and Rapamycin-Mediated Tumor Microenvironment Remodeling via mTOR Axis to Enhance Photodynamic Therapy

Photodynamic therapy (PDT) is expected to become a new type of adjuvant therapy for cancer owing to its advantages, such as noninvasive, high spatiotemporal selectivity, and fewer side effects. However, conventional organic photosensitizers can easily aggregate in a biological system, leading to decreased fluorescence quenching and reactive oxygen species. Furthermore, attributed to the inherent hypoxia and immunosuppressive properties of the complex tumor microenvironment (TME), the efficacy of PDT is severely restricted. Given this, groundbreaking work has constructed carrier-free self-assembled nanoplatforms (TNTP-Ra NPs) based on the newly synthesized zwitterionic PS-TNTP that has satisfactory image-guided PDT and offers a new vision for delivery of rapamycin with poor water solubility. Simultaneously, the coassembled rapamycin regulates the vigorous aerobic glycolysis of cancer cells and inhibits the expression of PD-L1 by targeting the mTOR axis to remold hypoxia and immunosuppression TME. Accordingly, the multifunctional nanoplatform integrating AIEgen-mediated PDT and TME remodeling is a forward-looking PDT design strategy.