Tumor-Selective Activation of Toll-Like Receptor 7/8 Agonist Nano-Immunomodulator Generates Safe Anti-Tumor Immune Responses upon Systemic Administration.
Angew Chem Int Ed Engl
; 61(52): e202214992, 2022 12 23.
Article
en En
| MEDLINE
| ID: mdl-36331428
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptor Toll-Like 7
/
Neoplasias
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article