Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 12, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202214992
Keywords
Glutathione-Responsiveness; Imidazoquinolines; Immunotherapy; Systemic Administration; Toll-Like Receptors
Categories
Funding
- Chinese post-doctoral international exchange program for a post-doctoral scholarship
- Shandong Provincial Natural Science Foundation
- National Natural Science Foundation of China
- [ZR2020QH350]
- [82003680]
- [82111530241]
Ask authors/readers for more resources
In this study, a polymeric nano-immunomodulator was developed to selectively activate the immune system in tumors, enhancing T lymphocyte infiltration without causing immune-related adverse effects. It shows promising potential for safe systemic targeting delivery.
Agonists of innate pattern recognition receptors such as toll-like receptors (TLRs) prime adaptive anti-tumor immunity and hold promise for cancer immunotherapy. However, small-molecule TLR agonists cause immune-related adverse effects (irAEs) after systemic administration. Herein, we report a polymeric nano-immunomodulator (cN@SS-IMQ) that is inactive until it is selectively metabolized to an active immunostimulant within the tumor. cN@SS-IMQ was obtained via self-assembly of a cyclo(Arg-Gly-Asp-D-Phe-Lys)-modified amphiphilic copolymeric prodrug. Upon systemic administration, cN@SS-IMQ preferentially accumulated at tumor sites and responded to high intracellular glutathione levels to release native imidazoquinolines for dendritic cell maturation, thereby enhancing the infiltration of T lymphocytes. Collectively, cN@SS-IMQ tends to activate the immune system without irAEs, thus suggesting its promising potential for safe systemic targeting delivery.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available