Obrador Elena, Jihad-Jebbar Ali, Salvador-Palmer Rosario, López-Blanch Rafael, Oriol-Caballo María, Moreno-Murciano María Paz, Navarro Enrique A, Cibrian Rosa, Estrela José M
Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain.
Scientia BioTech, 46002 Valencia, Spain.
Cancers (Basel). 2023 Jun 29;15(13):3413. doi: 10.3390/cancers15133413.
At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, developing more efficient heat nanomediators that may exhibit high specific absorption rates is still an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high-intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 µT, 4 h) or HT (52 °C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approximately 16%, 50%, and 21% of control values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol, and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated by combining EMFs, HT, and standard chemotherapy or EMFs, HT, and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that a combination of EMFs, HIFU-induced HT, standard chemotherapy, and a lysosomal permeabilizer induces a complete cancer regression.
目前，非电离辐射（NIR）在肿瘤治疗中的应用和疗效有限。在潜在联合应用方面，使用生物相容性磁性纳米颗粒作为热介质已得到广泛研究。然而，开发可能具有高比吸收率的更高效热纳米介质仍是一个未解决的问题。我们的目的是研究外部施加的磁场和热诱导近红外辐射是否会影响肿瘤细胞活力。为此，在体外条件下，将不同的人类癌细胞（A2058黑色素瘤、AsPC1胰腺癌、MDA-MB-231乳腺癌）用电磁场（EMF，使用螺线管）和热疗（HT，使用恒温浴）联合处理。还研究了近红外辐射与标准化疗和靶向治疗联合的效果。在体内测试了一种结合电磁场和高强度聚焦超声（HIFU）诱导热疗的实验装置。电磁场（25 μT，4小时）或热疗（52°C，40分钟）在体外对癌细胞活力的影响有限。然而，它们的联合分别使A2058、AsPC1和MDA-MB-231细胞的活力降至对照值的约16%、50%和21%。溶酶体通透性增加、组织蛋白酶释放到细胞质中以及线粒体依赖性细胞死亡激活是其潜在机制。通过将电磁场、热疗与标准化疗或电磁场、热疗与抗Hsp70靶向治疗联合，可以完全消除癌细胞。作为概念验证，在AsPC1异种移植模型中进行的体内实验表明，电磁场、HIFU诱导热疗、标准化疗和溶酶体通透剂的联合可导致癌症完全消退。
