Foglietta Federica, Panzanelli Patrizia, Serpe Loredana, Canaparo Roberto
Department of Drug Science and Technology, University of Torino, Via Pietro Giuria 13, 10125 Torino, Italy.
Department of Neuroscience Rita Levi Montalcini, University of Torino, Via Cherasco 15, 10126 Torino, Italy.
Biomedicines. 2022 Mar 6;10(3):615. doi: 10.3390/biomedicines10030615.
Sonodynamic therapy (SDT) is a noninvasive method for cancer treatment based on selective activation of a sonosensitiser by ultrasound (US), which results in the generation of reactive oxygen species (ROS) and cancer cell death. SDT uses a similar approach to photodynamic therapy (PDT), but can overcome the main drawback of PDT, i.e., poor tissue penetration of light. This research work investigated the anticancer effect of SDT on various two- (2D) and three-dimensional (3D) in vitro tumour models, using PDT as a reference treatment. Sonodynamic experiments were performed with pulsed US, specifically with shock waves (SW) and the prodrug 5-aminolevulinic acid (Ala), which is converted-at the mitochondrial level-into the sonosensitiser protoporphyrin IX (PPIX). SW-mediated PPIX sonodynamic activation resulted in a significant decrease in cell proliferation, especially on human fibrosarcoma (HT-1080) cells, where PPIX accumulation was higher compared to human melanoma (A2058) and neuroblastoma (SH-SY5 Y) cells. Moreover, SW-mediated SDT showed significant ROS generation, cell line-dependent in its amount, probably due to differences in Ala-induced PPIX synthesis. In all cancer cell lines, apoptosis was highlighted as the main cancer cell death pathway determined by SW-mediated SDT, along with significant cytochrome c release, and a consequent increase in DNA damage. The efficacy of SDT with SW and Ala in halting cancer cell proliferation was also confirmed in 3D cancer spheroids. The present study suggests that SW-mediated SDT is a valuable approach to slow down tumour proliferation, thus opening an innovative scenario in cancer treatment.
声动力疗法（SDT）是一种基于超声（US）对声敏剂的选择性激活来治疗癌症的非侵入性方法，这会导致活性氧（ROS）的产生和癌细胞死亡。SDT采用了与光动力疗法（PDT）类似的方法，但可以克服PDT的主要缺点，即光的组织穿透性差。本研究工作以PDT作为参考治疗方法，研究了SDT对各种二维（2D）和三维（3D）体外肿瘤模型的抗癌作用。使用脉冲超声，特别是冲击波（SW）和前药5-氨基乙酰丙酸（Ala）进行声动力实验，Ala在线粒体水平上转化为声敏剂原卟啉IX（PPIX）。SW介导的PPIX声动力激活导致细胞增殖显著降低，尤其是在人纤维肉瘤（HT-1080）细胞上，与人类黑色素瘤（A2058）和神经母细胞瘤（SH-SY5 Y）细胞相比，PPIX在该细胞中的积累更高。此外，SW介导的SDT显示出显著的ROS生成，其数量因细胞系而异，这可能是由于Ala诱导的PPIX合成存在差异。在所有癌细胞系中，细胞凋亡被认为是SW介导的SDT所确定的主要癌细胞死亡途径，同时伴随着细胞色素c的显著释放以及DNA损伤的相应增加。SW和Ala的SDT在阻止3D癌球中癌细胞增殖方面的功效也得到了证实。本研究表明，SW介导的SDT是减缓肿瘤增殖的一种有价值的方法，从而为癌症治疗开辟了一个创新的局面。
