AIEgen-Functionalized Mesoporous Silica Gated by Cyclodextrin-Modified CuS for Cell Imaging and Chemo-Photothermal Cancer Therapy

A novel multifunctional drug delivery system has been constructed by assembling per-6-thio-β-cyclodextrin-modified ultrasmall CuS nanoparticles (CD-CuS) onto fluorescent AIEgen-containing mesoporous silica nanoparticles (FMSN). The CD-CuS nanoparticles are anchored on the surface of benzimidazole-grafted FMSN, acting as a gatekeeper and photothermal agent. The prepared blue-emitting nanocomposite (FMSN@CuS) exhibits good biocompatibility and cell imaging capability. Anticancer drug doxorubicin hydrochloride (DOX) molecules are loaded into FMSN@CuS, and zero prerelease at physiological pH (7.4) and on-demand drug release at an acidic environment can be achieved due to the pH-responsive gate-opening of CD-CuS only at an acidic condition. The FMSN@CuS nanocomposite can generate obvious thermal effect after the exposure of 808 nm laser, which can also accelerate the DOX release. Meanwhile, the fluorescence intensity of DOX-loaded FMSN@CuS increases with the release of DOX, and the intracellular drug release process can be tracked according to the change of luminescence intensity. More importantly, DOX-loaded FMSN@CuS displays efficient anticancer effects in vitro upon 808 nm laser irradiation, demonstrating a good synergistic therapeutic effect via combining enhanced chemotherapy and photothermal therapy.