1. Programmable Delivery of Immune Adjuvant to Tumor-Infiltrating Dendritic Cells for Cancer Immunotherapy
- Author
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Jing Liu, Ya-Nan Fan, Yi-Fang Chen, Hongjun Li, Ying-Li Luo, Jin-Zhi Du, and Jun Wang
- Subjects
Guanine ,Phagocytosis ,medicine.medical_treatment ,Bioengineering ,02 engineering and technology ,Immunopotentiator ,Cancer immunotherapy ,Adjuvants, Immunologic ,Neoplasms ,medicine ,Humans ,General Materials Science ,Tumor microenvironment ,Chemistry ,Mechanical Engineering ,General Chemistry ,Dendritic cell ,Dendritic Cells ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,CpG site ,Cancer research ,Immunotherapy ,Nanocarriers ,0210 nano-technology ,Cpg odns - Abstract
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.
- Published
- 2020