Coordination and Redox Dual-Responsive Mesoporous Organosilica Nanoparticles Amplify Immunogenic Cell Death for Cancer Chemoimmunotherapy

Fan Zhang; Fangman Chen; Chao Yang; Lei Wang; Hanze Hu; Xuezhao Li; Xiao Zheng; Zheng Wang; Zhimin Chang; Tianyu Li; Li Li; Mingfeng Ge; Jinzhi Du; Wen Sun; Wen-Fei Dong; Dan Shao

doi:10.1002/smll.202100006

Coordination and Redox Dual-Responsive Mesoporous Organosilica Nanoparticles Amplify Immunogenic Cell Death for Cancer Chemoimmunotherapy

Small. 2021 Jul;17(26):e2100006. doi: 10.1002/smll.202100006. Epub 2021 Jun 3.

Authors

Fan Zhang^{1

2}, Fangman Chen^{1

2}, Chao Yang^{3

4}, Lei Wang⁵, Hanze Hu⁴, Xuezhao Li⁵, Xiao Zheng³, Zheng Wang², Zhimin Chang^{1

2}, Tianyu Li⁴, Li Li^{1

2}, Mingfeng Ge^{1

2}, Jinzhi Du⁶, Wen Sun⁵, Wen-Fei Dong^{1

2}, Dan Shao⁶

Affiliations

¹ School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
² CAS Key Laboratory of Bio Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
³ School of Biomedical Sciences and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510630, China.
⁴ Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
⁵ State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
⁶ Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 510006, China.

PMID: 34081391
DOI: 10.1002/smll.202100006

Abstract

Amplifying the chemotherapy-driven immunogenic cell death (ICD) for efficient and safe cancer chemoimmunotherapy remains a challenge. Here, a potential ICD nanoamplifier containing diselenide-bridged mesoporous organosilica nanoparticles (MONs) and chemotherapeutic ruthenium compound (KP1339) to achieve cancer chemoimmunotherapy is tailored. KP1339-loaded MONs show controlled drug release profiles via glutathione (GSH)-responsive competitive coordination and matrix degradation. High concentration of MONs selectively evoked reactive oxygen species production, GSH depletion, and endoplasmic reticulum stress in cancer cells, thus amplifying the ICD of KP1339 and boosting robust antitumor immunological responses. After the combination of PD-L1 checkpoint blockade, cancer cell membrane-cloaked KP1339-loaded MONs not only regress primary tumor growth with low systemic toxicity, but also inhibit distant tumor growth and pulmonary metastasis of breast cancer. The results have shown the potential of coordination and redox dual-responsive MONs boosting amplified ICD for cancer chemoimmunotherapy.

Keywords: chemoimmunotherapy; coordination-responsive drug release; diselenide bond; immunogenic cell-death; mesoporous organosilica nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Doxorubicin
Drug Carriers
Drug Delivery Systems
Humans
Immunogenic Cell Death
Nanoparticles*
Neoplasms* / drug therapy
Oxidation-Reduction

Substances

Drug Carriers
Doxorubicin