Sonopermeation combined with stroma normalization enables complete cure using nano-immunotherapy in murine breast tumors DOI Creative Commons

Constantina Neophytou,

Antonia Charalambous, Chrysovalantis Voutouri

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113722 - 113722

Published: April 1, 2025

Nano-immunotherapy shows great promise in improving patient outcomes, as seen advanced triple-negative breast cancer, but it does not cure the disease, with median survival under two years. Therefore, understanding resistance mechanisms and developing strategies to enhance its effectiveness cancer is crucial. A key mechanism pronounced desmoplasia tumor microenvironment, which leads dysfunction of blood vessels thus, hypoperfusion, limited drug delivery hypoxia. Ultrasound sonopermeation agents that normalize stroma have been employed separately restore vascular abnormalities tumors some success. Here, we performed vivo studies murine, orthotopic models explore if combination ultrasound a normalization can synergistically improve perfusion efficacy nano-immunotherapy. We found proposed combinatorial treatment drastically reduce primary growth many cases were no longer measurable. Overall showed all mice received survived rechallenge experiments revealed survivors obtained immunological memory. Employing elastography contrast enhanced along proteomics analysis, flow cytometry immunofluorescene staining, reduced stiffness normal levels, restoring oxygenation. Furthermore, increased infiltration activity immune cells altered levels immunosupportive chemokines. Finally, using machine learning identified stiffness, CD8+ T M2-type macrophages strong predictors response.

Language: Английский

Sonopermeation combined with stroma normalization enables complete cure using nano-immunotherapy in murine breast tumors DOI Creative Commons

Constantina Neophytou,

Antonia Charalambous, Chrysovalantis Voutouri

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113722 - 113722

Published: April 1, 2025

Nano-immunotherapy shows great promise in improving patient outcomes, as seen advanced triple-negative breast cancer, but it does not cure the disease, with median survival under two years. Therefore, understanding resistance mechanisms and developing strategies to enhance its effectiveness cancer is crucial. A key mechanism pronounced desmoplasia tumor microenvironment, which leads dysfunction of blood vessels thus, hypoperfusion, limited drug delivery hypoxia. Ultrasound sonopermeation agents that normalize stroma have been employed separately restore vascular abnormalities tumors some success. Here, we performed vivo studies murine, orthotopic models explore if combination ultrasound a normalization can synergistically improve perfusion efficacy nano-immunotherapy. We found proposed combinatorial treatment drastically reduce primary growth many cases were no longer measurable. Overall showed all mice received survived rechallenge experiments revealed survivors obtained immunological memory. Employing elastography contrast enhanced along proteomics analysis, flow cytometry immunofluorescene staining, reduced stiffness normal levels, restoring oxygenation. Furthermore, increased infiltration activity immune cells altered levels immunosupportive chemokines. Finally, using machine learning identified stiffness, CD8+ T M2-type macrophages strong predictors response.

Language: Английский

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