期刊
BIOMATERIALS
卷 258, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120275
关键词
CRISPR/Cas9; Immunotherapy; Gene therapy; Virus-like nanoparticle; Co-delivery system
资金
- National Key Research and Development Programs of China (China) [2018YFA0209700]
- National Natural Science Foundation of China (China
- NSFC) [51673100, 21620102005]
- Tianjin Municipal Science and Technology Commission Project (China) [15ZXLCSY00060, 15ZXJZSY00040]
- Fundamental Research Funds for the Central Universities (China
- Nankai University) [ZB19100123, ZB16008705]
- Tianjin Natural Science Foundation (China) [18JCQNJC03600]
The Clustered Regularly Interspaced Short Palindmmic Repeats (CRISPR)-associated protein 9 (Cas9) system holds great promise for the cancer gene therapy. However, due to complicated signal networks and various compensatory mechanisms in tumors, adjusting a single molecular pathway has limited effects on cancer treatments. Herein, a virus-like nanoparticle (VLN) was reported as a versatile nanoplatform to co-deliver CRISPR/Cas9 system and small molecule drugs for effective malignant cancer treatment. VLN has a core-shell structure, in which small molecule drugs and CRISPR/Cas9 system are loaded in the mesoporous silica nanoparticle (MSN)-based core, which is further encapsulated with a lipid shell. This structure allows VLN maintaining stable during blood circulation. As reaching tumors, VLN releases the CRISPR/Cas9 system and small molecule drugs in response to the reductive microenvimnment, resulting in the synergistic regulation of multiple cancer-associated pathways. By loading a single guide RNA (sgRNA) targeting programmed death-ligand 1 and axitinib, VLN achieved to disrupt multiple immunosuppressive pathways and suppress the growth of melanoma in vivo. More importantly, VLN can co-deliver almost any combination of sgRNAs and small molecule drugs to tumors, suggesting the great potential of VLN as a general platform for the development of advanced combination therapies against malignant tumors.
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