Therapeutic liposomal combination to enhance chemotherapy response and immune activation of tumor microenvironment.
J Control Release
; 373: 38-54, 2024 Sep.
Article
de En
| MEDLINE
| ID: mdl-38986909
ABSTRACT
Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co-loaded with TLR agonists Poly IC and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Danio zébré
/
Microenvironnement tumoral
/
Oxaliplatine
/
Liposomes
/
Macrophages
/
Antinéoplasiques
Limites:
Animals
Langue:
En
Journal:
J Control Release
Sujet du journal:
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Pays-Bas
Pays de publication:
Pays-Bas