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Drug Des Devel Ther ; 18: 1833-1853, 2024.
Article de Anglais | MEDLINE | ID: mdl-38828018

RÉSUMÉ

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.


Sujet(s)
Lymphocytes T CD8+ , Prolifération cellulaire , Chimiokine CXCL10 , Tumeurs du côlon , Souris de lignée BALB C , Tumeurs du côlon/immunologie , Tumeurs du côlon/anatomopathologie , Tumeurs du côlon/traitement médicamenteux , Animaux , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/effets des médicaments et des substances chimiques , Souris , Prolifération cellulaire/effets des médicaments et des substances chimiques , Chimiokine CXCL10/métabolisme , Chimiokine CXCL10/immunologie , Membrane bactérienne externe/immunologie , Membrane bactérienne externe/effets des médicaments et des substances chimiques , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Humains , Tumeurs expérimentales/anatomopathologie , Tumeurs expérimentales/immunologie , Tumeurs expérimentales/traitement médicamenteux , Tests de criblage d'agents antitumoraux , Cellules cancéreuses en culture
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