非热声增强顺铂对小鼠异种移植宫颈癌的化疗效果。
Non-thermal Acoustic Enhancement of Chemotherapeutic Effects of Cisplatin on Xenografted Cervical Cancer in Mice.
发表日期:2023 Nov
作者:
Seung-Schik Yoo, Perry Katsarakes, Jason Gashi, Evgenii Kim, Hyun-Chul Kim, Mark Böhlke
来源:
Cellular & Molecular Immunology
摘要:
我们使用异种移植人宫颈癌的小鼠模型检查了低强度聚焦超声 (FUS) 对从血浆蛋白中解离顺铂并增强其化疗效果的影响。FUS 以脉冲模式运行,应用于浸入水中的透析盒。含有牛血清白蛋白(BSA)和顺铂的生理盐水浴,并测量扩散到盒中的顺铂的未结合水平。为了评估该技术的体内功效,在四种不同的组合条件下,在给予或不给予顺铂和 FUS 的情况下,给无胸腺 nu/nu 小鼠接种人宫颈癌细胞。腹腔注射顺铂后,FUS 在 10 天的四个独立疗程中被递送至肿瘤块 1 小时。体外平衡透析显示,与盒式磁带相比,FUS 的非热应用增加了未结合顺铂的浓度。没有暴露于超声处理,表明成功解绑。体内肿瘤生长评估表明,给予顺铂后的 FUS 导致肿瘤生长显着减少,而单独给予顺铂则表现出平台生长。在不施用顺铂的情况下,无论是否应用 FUS,都观察到相同的侵袭性肿瘤生长速率。脉冲应用 FUS 可以使顺铂与白蛋白解离,并增强其在宫颈癌中的杀肿瘤作用。需要进一步评估肿瘤内/全身顺铂浓度,以量化其对肿瘤的选择性递送。版权所有 © 2023 国际抗癌研究所(George J. Delinasios 博士),保留所有权利。
We examined the effect of low-intensity focused ultrasound (FUS) on unbinding cisplatin from plasma proteins and enhancing its chemotherapeutic efficacy using a mouse model of xenograft human cervical cancer.FUS, operating in a pulsed mode, was applied to a dialysis cassette immersed in a normal saline bath containing both bovine serum albumin (BSA) and cisplatin, and the unbound level of cisplatin diffused into the cassette was measured. To assess the in vivo efficacy of the technique, athymic nu/nu mice were inoculated with human cervical cancer cells under four different combinatory conditions, with and without the administration of cisplatin and FUS. FUS was delivered to the tumor mass for 1 h across four separate sessions spanning a period of 10 days, following the intraperitoneal injection of cisplatin.In vitro equilibrium dialysis revealed that non-thermal application of FUS increased the concentration of unbound cisplatin compared to cassettes that were not exposed to sonication, suggesting successful unbinding. Assessment of tumor growth in vivo showed that FUS following cisplatin administration resulted in a significant reduction in tumor growth, whereas the administration of cisplatin alone exhibited plateau growth. Without administration of cisplatin, equivalent rates of aggressive tumor growth were observed regardless of the application of FUS.Pulsed application of FUS can unbind cisplatin from albumin and enhance its tumoricidal effects in cervical cancer. Further assessment of intratumoral/systemic cisplatin concentration is required to quantify its selective delivery to the tumor.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.