We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tumor‐Selective Activation of Toll‐Like Receptor 7/8 Agonist Nano‐Immunomodulator Generates Safe Anti‐Tumor Immune Responses upon Systemic Administration.
- Authors
Hao, Yanyun; Li, Hui; Ge, Xiaoyan; Liu, Yang; Li, Xia; Liu, Yutong; Chen, Hongfei; Zhang, Shiying; Zou, Jing; Huang, Lingling; Zhao, Fabao; Kang, Dongwei; De Geest, Bruno G.; Zhang, Zhiyue
- Abstract
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.
- Subjects
IMMUNE response; T cells; IMMUNE system; DENDRITIC cells; PATTERN perception receptors
- Publication
Angewandte Chemie, 2022, Vol 134, Issue 52, p1
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202214992