Supramolecular nanomaterials based on hollow mesoporous drug carriers and macrocycle-capped CuS nanogates for synergistic chemo-photothermal therapy

Multifunctional supramolecular nanoplatforms that integrate the advantages of different therapeutic techniques can trigger multimodal synergistic treatment of tumors, thus representing an emerging powerful tool for cancer therapeutics. Methods: In this work, we design and fabricate a multifunctional supramolecular drug delivery platform, namely Fa-mPEG@CP5-CuS@HMSN-Py nanoparticles (FaPCH NPs), consisting of a pyridinium (Py)-modified hollow mesoporous silica nanoparticles-based drug reservoir (HMSN-Py) with high loading capacity, a layer of NIR-operable carboxylatopillar[5]arene (CP5)-functionalized CuS nanoparticles (CP5-CuS) on the surface of HMSN-Py connected through supramolecular host-guest interactions between CP5 rings and Py stalks, and another layer of folic acid (Fa)-conjugated polyethylene glycol (Fa-PEG) antennas by electrostatic interactions capable of active targeting at tumor lesions, in a controlled, highly integrated fashion for synergistic chemo-photothermal therapy. Results: Fa-mPEG antennas endowed the enhanced active targeting effect toward cancer cells, and CP5-CuS served as not only a quadruple-stimuli responsive nanogate for controllable drug release but also a special agent for NIR-guided photothermal therapy. Meanwhile, anticancer drug doxorubicin (DOX) could be released from the HMSN-Py reservoirs under tumor microenvironments for chemotherapy, thus realizing multimodal synergistic therapeutics. Such a supramolecular drug delivery platform showed effective synergistic chemo-photothermal therapy both in vitro and in vivo. Conclusion: This novel supramolecular nanoplatform possesses great potential in controlled drug delivery and tumor cellular internalization for synergistic chemo-photothermal therapy, providing a promising approach for multimodal synergistic cancer treatment.