Theranostics:纳米热疗法或可软化肿瘤,提高癌症靶向疗法的治疗效率

Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

肿瘤的机械阻力和标准疗法的附带损伤往往会阻碍抵御癌症的效果，近日，来自法国国家健康与医学研究所等机构的研究人员通过对肿瘤加热成功软化了恶性肿瘤，这种方法称之为纳米热疗法，其能够让肿瘤对治疗制剂更加敏感，相关研究刊登于国际杂志Theranostics上。

Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects.On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment.