期刊
ACS APPLIED MATERIALS & INTERFACES
卷 12, 期 14, 页码 16018-16030出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b23084
关键词
immunochemotherapy; PD-L1; CRISPR/Cas9; nanoparticle; immunogenic cell death
资金
- National Natural Science Foundation of China [81673374, 81872810]
- Program for HUST Academic Frontier Youth Team [2018QYTD13]
Blocking immune checkpoints with monoclonal antibody has been verified to achieve potential clinical successes for cancer immunotherapy. However, its application has been impeded by the cold tumor microenvironment. Here, weak acidity-responsive nanoparticles co-loaded with CRISPR/Cas9 and paclitaxel (PTX) with the ability to convert cold tumor into hot tumor are reported. The nanoparticles exhibited high cargo packaging capacity, superior transfection efficiency, well bio-compatibility, and effective tumor accumulation. The CRISPR/Cas9 encapsulated in nanoparticles could specifically knock out cyclin-dependent kinase 5 gene to significantly attenuate the expression of programmed death-ligand 1 on tumor cells. More importantly, PTX co-delivered in nanoparticles could significantly induce immunogenic cell death, reduce regulatory T lymphocytes, repolarize tumor-associated macrophages, and enhance antitumor immunity. Therefore, the nanoparticles could effectively convert cold tumor into hot tumor, achieve effective tumor growth inhibition, and prolong overall survival from 16 to 36 days. This research provided a referable strategy for the development of combinatorial immunotherapy and chemotherapy.
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