Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 13, Issue -, Pages 3661-3677Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S167407
Keywords
periodic mesoporous organosilica; CuS; triple-responsive release; chemophotothermal therapy
Funding
- National Natural Science Foundation of China [81772433]
- Science and Technology Commission of Shanghai Municipality [16411972200]
- project of Shanghai Municipal Health Bureau [201540100]
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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 chemophotothermal 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.
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