Photothermal Depletion of Cancer-Associated Fibroblasts Normalizes Tumor Stiffness in Desmoplastic Cholangiocarcinoma

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 desm...

Full description

Saved in:
Bibliographic Details
Published in:ACS nano 2020-05, Vol.14 (5), p.5738-5753
Main Authors: Nicolás-Boluda, Alba, Vaquero, Javier, Laurent, Gautier, Renault, Gilles, Bazzi, Rana, Donnadieu, Emmanuel, Roux, Stéphane, Fouassier, Laura, Gazeau, Florence
Format: Article
Language:English
Subjects:
Bile Duct Neoplasms - therapy
Bile Ducts, Intrahepatic
Cancer
Cancer-Associated Fibroblasts
Chemical Sciences
Cholangiocarcinoma - therapy
Fibroblasts
Gold
Humans
Life Sciences
Metal Nanoparticles
Tumor Microenvironment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.0c00417