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Angew Chem Int Ed Engl ; 63(23): e202401250, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38576254

RESUMEN

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.


Asunto(s)
Imidas , Factores Inmunológicos , Inmunoterapia , Naftalenos , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Humanos , Naftalenos/química , Naftalenos/farmacología , Imidas/química , Imidas/farmacología , Animales , Nanopartículas/química , Ratones , Microambiente Tumoral/efectos de los fármacos , Terapia Fototérmica , Imidazoles/química , Imidazoles/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Línea Celular Tumoral
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