超声介导的细胞膜透化-超声穿孔,增强药物直接递送到肿瘤部位,同时减少全身副作用。超声增强细胞内钙摄取的潜力-细胞死亡和增殖的关键调节剂-为传统化疗提供了创新的替代方案。然而,在超声穿孔研究中,钙治疗应用仍未充分开发。本研究提供了钙超声穿孔(CaSP)的综合分析,结合了钙离子和SonoVue微泡的超声治疗,对胃肠道癌细胞LoVo和HPAF-II。最初,确定了最佳声穿孔参数:1MHz频率的声波,占空比为50%,强度为2W/cm2。随后,各种细胞生物效应,比如生存能力,氧化应激,新陈代谢,线粒体功能,扩散,和细胞死亡,在CaSP治疗后进行评估。CaSP通过诱导氧化和代谢应激显著损害癌细胞功能,线粒体去极化增加,降低ATP水平,并以Ca2+剂量依赖性方式升高葡萄糖摄取,导致内在凋亡途径的激活。细胞对CaSP的反应取决于TP53基因的突变状态:结肠癌细胞更容易受到CaSP诱导的凋亡和G1期细胞周期停滞的影响,而胰腺癌细胞显示更高的坏死反应和G2细胞周期停滞。这些有希望的结果鼓励未来的研究,以优化临床使用的声孔参数,研究与现有治疗的协同作用,并评估体内长期安全性和有效性。我们的研究强调了CaSP在癌症治疗中提高安全性和有效性的临床潜力。对制药和生物医学领域具有重要意义。
Ultrasound-mediated cell membrane permeabilization -
sonoporation, enhances drug delivery directly to tumor sites while reducing systemic side effects. The potential of ultrasound to augment intracellular calcium uptake - a critical regulator of cell death and proliferation - offers innovative alternative to conventional chemotherapy. However, calcium therapeutic applications remain underexplored in
sonoporation studies. This research provides a comprehensive analysis of calcium
sonoporation (CaSP), which combines ultrasound treatment with calcium ions and SonoVue microbubbles, on gastrointestinal cancer cells LoVo and HPAF-II. Initially, optimal
sonoporation parameters were determined: an acoustic wave of 1 MHz frequency with a 50 % duty cycle at intensity of 2 W/cm2. Subsequently, various cellular bioeffects, such as viability, oxidative stress, metabolism, mitochondrial function, proliferation, and cell death, were assessed following CaSP treatment. CaSP significantly impaired cancer cell function by inducing oxidative and metabolic stress, evidenced by increased mitochondrial depolarization, decreased ATP levels, and elevated glucose uptake in a Ca2+ dose-dependent manner, leading to activation of the intrinsic apoptotic pathway. Cellular response to CaSP depended on the TP53 gene\'s mutational status: colon cancer cells were more susceptible to CaSP-induced apoptosis and G1 phase cell cycle arrest, whereas pancreatic cancer cells showed a higher necrotic response and G2 cell cycle arrest. These promising results encourage future research to optimize
sonoporation parameters for clinical use, investigate synergistic effects with existing treatments, and assess long-term safety and efficacy in vivo. Our study highlights CaSP\'s clinical potential for improved safety and efficacy in cancer therapy, offering significant implications for the pharmaceutical and biomedical fields.