Yin Junkai, Wu Kaijie, Yu Yun, Zhong Yuan, Song Zihua, Chang Chao, Liu Guozhi
Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China.
School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
ACS Nano. 2024 Feb 13;18(6):4796-4810. doi: 10.1021/acsnano.3c09216. Epub 2024 Jan 23.
Telomeres are nanoscale DNA-protein complexes to protect and stabilize chromosomes. The reexpression of telomerase in cancer cells is a key determinant crucial for the infinite proliferation and long-term survival of most cancer cells. However, the use of telomerase inhibitors for cancer treatment may cause problems such as poor specificity, drug resistance, and cytotoxicity. Here, we discovered a nondrug and noninvasive terahertz modulation strategy capable of the long-term suppression of cancer cells by inhibiting telomerase activity. First, we found that an optimized frequency of 33 THz photon irradiation effectively inhibited the telomerase activity by molecular dynamics simulation and frequency filtering experiments. Moreover, experiments showed that telomerase activity in 4T1 and MCF-7 cells significantly decreased by 77% and 80% respectively, after 21 days of regular 33 THz irradiation. Furthermore, two kinds of cells were found to undergo aging, apoptosis, and DNA double-strand breaks caused by telomere crisis, which seriously affected the survival of cancer cells. In addition, the tumorigenicity of 4T1 cells irradiated with 33 THz waves for 21 days in mice decreased by 70%. In summary, this study demonstrates the potential application of THz modulation in nano therapy for cancer.
端粒是纳米级的DNA-蛋白质复合物,用于保护和稳定染色体。癌细胞中端粒酶的重新表达是大多数癌细胞无限增殖和长期存活的关键决定因素。然而,使用端粒酶抑制剂进行癌症治疗可能会导致特异性差、耐药性和细胞毒性等问题。在此,我们发现了一种非药物、非侵入性的太赫兹调制策略,能够通过抑制端粒酶活性长期抑制癌细胞。首先,我们通过分子动力学模拟和频率过滤实验发现,优化后的33太赫兹光子照射频率能有效抑制端粒酶活性。此外,实验表明,经过21天的常规33太赫兹照射后,4T1和MCF-7细胞中的端粒酶活性分别显著降低了77%和80%。此外,发现两种细胞会经历由端粒危机引起的衰老、凋亡和DNA双链断裂,这严重影响了癌细胞的存活。另外,用33太赫兹波照射21天的4T1细胞在小鼠体内的致瘤性降低了70%。总之,本研究证明了太赫兹调制在癌症纳米治疗中的潜在应用。