Photothermal Depletion of Cancer-Associated Fibroblasts Normalizes Tumor Stiffness in Desmoplastic Cholangiocarcinoma (Équipe Housset)

28 - Avril - 2020

Alba Nicolás-Boluda, Javier Vaquero, Gautier Laurent, Gilles Renault, Rana Bazzi, Emmanuel Donnadieu, Stéphane Roux, Laura Fouassier, Florence Gazeau

ACS Nano. 2020;14(5):5738-53

Physical oncology recognizes tissue stiffness mediated by activation of cancer-associated fibroblasts (CAF) and extracellular matrix remodeling as an active modulator of tumorigenesis, treatment resistance, and clinical outcome. Cholangiocarcinoma (CCA) is a highly aggressive and chemoresistant desmoplastic cancer enriched in CAF. CCA's stroma mechanical properties are considered responsible for its chemoresistant character. To normalize tumor mechanics, we propose a physical strategy based on remotely light-activated nanohyperthermia to modulate the tumor microenvironment. In this study, we report the use of multifunctional iron oxide nanoflowers decorated with gold nanoparticles (GIONF) as efficient nanoheaters to achieve complete tumor regression following three sessions of mild hyperthermia. The preferential uptake of GIONF by CAF allowed targeting this cell population, which resulted in a significant early reduction of tumor stiffness followed by tumor regression. In conclusion, our study highlights a spatially and temporally controlled physical strategy, GIONF-mediated photothermal therapy to deplete CAF and normalize the tumor mechanics that may apply to desmoplastic cancer and CCA treatment.

Hôpital St-Antoine

Bâtiment Kourilsky
34 rue Crozatier
75012 PARIS

Sorbonne Université
27 rue Chaligny
75012 PARIS

Ce site utilise des cookies et vous donne le contrôle sur ce que vous souhaitez activer Tout accepter Personnaliser