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Nat Commun ; 12(1): 1999, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790276

RESUMEN

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.


Asunto(s)
Imidazoles/uso terapéutico , Inmunoterapia/métodos , Nanopartículas/uso terapéutico , Neoplasias/terapia , Microambiente Tumoral/efectos de los fármacos , Animales , Plaquetas/química , Plaquetas/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Células Cultivadas , Femenino , Células HT29 , Humanos , Imidazoles/química , Imidazoles/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Ratones Endogámicos C57BL , Nanopartículas/química , Neoplasias/inmunología , Neoplasias/patología , Resultado del Tratamiento , Microambiente Tumoral/inmunología
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