Fabrication of multifunctional triple-responsive platform based on CuS-capped periodic mesoporous organosilica nanoparticles for chemo-photothermal therapy

Introduction For an ideal drug delivery system, the outstanding drug-loading capacity and specific control of the release of therapeutics at the desired lesions are crucial. In this work, we developed a triple-responsive nanoplatform based on copper sulfide (CuS)-capped yolk−shell-structured periodic mesoporous organosilica nanoparticles (YSPMOs) for synergetic chemo-photothermal therapy.Methods Herein, the YSPMOs were employed as a drug carrier, which exhibited a high doxorubicin (DOX) loading capacity of 386 mg/g. In this controlled-release drug delivery system, CuS serves as a gatekeeper to modify YSPMOs with reduction-cleavable disulfide bond (YSPMOs@CuS). CuS could not only avoid premature leakage in the delivery process, but also endowed the excellent photothermal therapy (PTT) ability.Results Upon entering into cancer cells, the CuS gatekeeper was opened with the breaking of disulfide bonds and the DOX release from YSPMOs(DOX)@CuS in response to the intracellular acidic environment and external laser irradiation. Such a precise control over drug release, combined with the photothermal effect of CuS nanoparticles, is possessed by synergistic chemo-photothermal therapy for cancer treatment. Both in vitro and in vivo experimental data indicated that the synergistic effect of YSPMOs(DOX)@CuS showed efficient antitumor effect. In addition, low systemic toxicity was observed in the pathologic examinations of liver, spleen, lungs, and kidneys.Conclusion This versatile nanoplatform combination of PTT, chemotherapeutics, and gating components shows general potential for designing multifunctional drug delivery systems.