Synergistically Enhancing Tumor Chemotherapy Using an Aggregation-Induced Emission Photosensitizer on Covalently Conjugated Molecularly Imprinted Polymer Nanoparticles

Due to the polygenic and heterogeneous nature of the tumorigenesis process, traditional chemotherapy is far from desirable. Fabricating multifunctional nanoplatforms integrating photodynamic effect can synergistically enhance chemotherapy because they can make the cancer cells much sensitive to chemotherapeutics. However, how to assemble different units in nanoplatforms and minimize side effects caused by chemodrugs and photosensitizers (PSs) still needs to be explored. Herein, a nanoplatform CPP/PS-MIP@DOX is developed using a simultaneously covalently conjugated new aggregation-induced emission (AIE) PS and a cell-penetrating peptide (CPP) on the surface of silica-based molecularly imprinted polymer (MIP) nanoparticles, prepared with doxorubicin (DOX) as the template in the water system via a sol-gel technique. CPP/PS-MIP@DOX has good biocompatibility, high DOX-loading ability, promoted cellular uptake, and sustained and pH-sensitive drug release capability. Furthermore, it can efficiently penetrate into tumor tissue, accurately home to, and accumulate at the tumor site. As a result, a better efficacy with lower cytotoxicity is achieved with a smaller dosage of DOX by utilizing either the photodynamic effect or unique characteristics of the MIP. It is the first nanoplatform fabricated by chemically conjugating AIE PSs directly on the surface of the scaffold via the surface-decorated strategy and successfully applied in cancer therapy. This work provides an effective strategy by constructing AIE PS-based cancer nanomedicines with MIPs as scaffolds.