Lymph-Node-Targeted Cholesterolized TLR7 Agonist Liposomes Provoke a Safe and Durable Antitumor Response.
Nano Lett
; 21(19): 7960-7969, 2021 10 13.
Article
em En
| MEDLINE
| ID: mdl-34533963
ABSTRACT
Toll-like receptor (TLR) agonists as the potent stimulants of an innate immune system hold promises for applications in anticancer immunotherapy. However, most of them are limited in the clinical translation due to the uncontrolled systemic inflammatory response. In the current study, 1V209, a small molecule TLR7 agonist, was conjugated with cholesterol (1V209-Cho) and prepared into liposomes (1V209-Cho-Lip). 1V209-Cho-Lip exerted minimal toxic effects and enhanced the transportation ability in lymph nodes (LNs) compared with 1V209. 1V209-Cho-Lip treatment inhibited tumor progression in CT26 colorectal cancer, 4T1 breast cancer, and Pan02 pancreatic ductal cancer models through inducing effective DC activation and eliciting CD8+ T cell responses. Furthermore, 1V209-Cho-Lip induced tumor-specific memory immunity to inhibit cancer recurrence and metastasis. These results indicate that cholesterol conjugation with 1V209 is an effective approach to target lymph nodes and to reduce the adverse effects. This work provides a rational basis for the distribution optimization of TLR agonists for potential clinical use.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor 7 Toll-Like
/
Lipossomos
Limite:
Animals
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2021
Tipo de documento:
Article