Journal
ADVANCED MATERIALS
Volume 32, Issue 50, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202004385
Keywords
biodegradable mesoporous organosilica nanoparticles; biomimetic; chemo‐ immunotherapy; diselenide bonds; X‐ ray radiation responsivity
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Funding
- National Natural Science Foundation of China [81902166, 81771982, 81601609, 61535010, 8160071152]
- National Key R&D Program of China [2017YFF0108600, 2017YFC0211900]
- Natural Science Foundation of Jiangsu Province [BK20181236, BE2019683]
- Science and Technology Department of Jinan City [2018GXRC016]
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Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.
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