Nicolás-Boluda Alba, Vaquero Javier, Laurent Gautier, Renault Gilles, Bazzi Rana, Donnadieu Emmanuel, Roux Stéphane, Fouassier Laura, Gazeau Florence
Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris, CNRS-UMR 7057, Paris 75013, France.
Institut Cochin, Université de Paris, INSERM U1016/CNRS UMR 8104, Paris 75014, France.
ACS Nano. 2020 May 26;14(5):5738-5753. doi: 10.1021/acsnano.0c00417. Epub 2020 May 6.
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.
物理肿瘤学认识到，由癌症相关成纤维细胞（CAF）激活和细胞外基质重塑介导的组织硬度是肿瘤发生、治疗抗性和临床结果的一种主动调节因子。胆管癌（CCA）是一种富含CAF的高侵袭性和化疗耐药性的促结缔组织增生性癌症。CCA的基质力学特性被认为是其化疗耐药特性的原因。为了使肿瘤力学正常化，我们提出了一种基于远程光激活纳米热疗的物理策略，以调节肿瘤微环境。在本研究中，我们报告了使用装饰有金纳米颗粒的多功能氧化铁纳米花（GIONF）作为高效纳米加热器，在三次温和热疗后实现肿瘤完全消退。CAF对GIONF的优先摄取允许靶向该细胞群体，这导致肿瘤硬度在早期显著降低，随后肿瘤消退。总之，我们的研究强调了一种空间和时间可控的物理策略，即GIONF介导的光热疗法，以消耗CAF并使肿瘤力学正常化，这可能适用于促结缔组织增生性癌症和CCA的治疗。
