期刊
NANO LETTERS
卷 20, 期 7, 页码 4882-4889出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c00893
关键词
cancer immunotherapy; tumor microenvironment; dendritic cell; nanoadjuvant; cytosine-guanine
类别
资金
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [51633008, 51903089]
- Young Elite Scientists Sponsorship Program by CAST [2018QNRC001]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S054]
- Guangdong Provincial Pearl River Talents Program [2017GC010713]
- Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.
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