Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy

作者：Shao, Dan^*; Zhang, Fan; Chen, Fangman; Zheng, Xiao; Hu, Hanze; Yang, Chao; Tu, Zhaoxu; Wang, Zheng; Chang, Zhimin; Lu, Junna; Li, Tianyu; Zhang, Yuan; Chen, Li; Leong, Kam W.^*; Dong, Wen-fei^*

来源：Advanced Materials, 2020, 32(50): 2004385.

DOI：10.1002/adma.202004385

• biodegradable mesoporous organosilica nanoparticles
• biomimetic
• chemo&#8208
• immunotherapy
• diselenide bonds
• X&#8208
• ray radiation responsivity

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.

• 单位
  中国科学院; 吉林大学