期刊
ADVANCED MATERIALS
卷 33, 期 12, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202006003
关键词
CRISPR; Cas9; gene delivery; immune checkpoint blockade; immunogenic cell death; nanomedicine
类别
资金
- National Natural Science Foundation of China [82073779, 81872807, 81573003]
- Fundamental Research Funds for the Central Universities [2018XZZX001-14]
- Natural Science Foundation of Zhejiang Province (Distinguished Young Scholar Program) [LR21H300002]
- Association Foundation of Zhejiang Natural Science Foundation-Zhejiang Society for Mathematical Medicine [LSY19H160005]
- National Key Research and Development Program of China [2018YFA0901800]
- Leading Talent of Ten Thousand Plan - National High-Level Talents Special Support Plan
The photothermal genome-editing strategy using a supramolecular cationic gold nanorod for CRISPR/Cas9 delivery to disrupt PD-L1 and induce immunogenic cell death (ICD) shows promising results in improving immune checkpoint blockade (ICB) therapy. This approach enhances dendritic cell conversion to T cells, promotes infiltration of cytotoxic T lymphocytes into tumors, and reprograms the immunosuppressive tumor microenvironment into an immunoactive one to inhibit primary and metastatic tumor activity with long-term immune memory effects.
A photothermal genome-editing strategy is described to improve immune checkpoint blockade (ICB) therapy by CRISPR/Cas9-mediated disruption of PD-L1 and mild-hyperthermia-induced activation of immunogenic cell death (ICD). This strategy relies on a supramolecular cationic gold nanorod that not only serves as a carrier to deliver CRISPR/Cas9 targeting PD-L1, but also harvests the second near-infrared-window (NIR-II) light and converts into mild hyperthermia to induce both ICD and gene expression of Cas9. The genomic disruption of PD-L1 significantly augments ICB therapy by improving the conversion of dendritic cells to T cells, followed by promoting the infiltration of cytotoxic T lymphocytes into tumors, thereby reprogramming immunosuppressive tumor microenvironment into immunoactive one. Such a therapeutic modality greatly inhibits the activity of primary and metastatic tumors and exhibits long-term immune memory effects against both rechallenged and recurrent tumors. The current therapeutic strategy for synergistic PD-L1 disruption and ICD activation represents an appealing way for cancer immunotherapy.
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