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Dosimetric assessment of antitumor treatment by enhanced bleomycin delivery via electroporation and sonoporation
Bioelectrochemistry ( IF 4.8 ) Pub Date : 2022-05-07 , DOI: 10.1016/j.bioelechem.2022.108153
Martynas Maciulevičius 1 , Mindaugas Tamošiūnas 2 , Rytis Jurkonis 3 , Saulius Šatkauskas 1
Affiliation  

Targeted and controlled techniques of intratumoral delivery of chemotherapeutic agents are under extensive development, since they diminish detrimental side-effects of conventional anticancer drugs.

We investigated the effectiveness of chemotherapy using bleomycin (1 mg/ml) and Sonovue microbubbles combined with: electroporation (EP), mainly designed for subcutaneous tumor therapy, and sonoporation (SP) - for deeper localized tumors. Research was performed on hepatoma MH-22A tumors in murine models, exposed to EP or SP and combined (EP + SP) treatment.

Animal survival time and the rate/ speed of tumor growth reduction were examined. Study demonstrated that both EP or SP and their combination (EP + SP) were able to induce the reduction of tumor volume from the 3rd day after treatment. The employment of EP before SP allowed to significantly reduce the values of inertial cavitation dose (ICD), necessary to induce complete tumor reduction and prolong animal survival.

The analysis of ultrasound (US) side-scattered signals and B-scan imaging indicated the occurrence of inertial cavitation at our experimental conditions. Strong (R2 = 0.88; p < 0.0001) correlation of ICD with the survival time of corresponding unrecovered mice indicates the option for the dosimetric control and standardization of cavitation activities for in vivo practice.



中文翻译:

通过电穿孔和声穿孔增强博莱霉素递送对抗肿瘤治疗的剂量学评估

化疗药物的肿瘤内递送的靶向和受控技术正在广泛开发中,因为它们减少了常规抗癌药物的有害副作用。

我们研究了使用博莱霉素 (1 mg/ml) 和 Sonovue 微泡联合以下疗法的化疗效果:电穿孔 (EP),主要设计用于皮下肿瘤治疗,以及声穿孔 (SP) - 用于更深的局部肿瘤。在小鼠模型中对肝癌 MH-22A 肿瘤进行了研究,暴露于 EP 或 SP 和联合 (EP + SP) 治疗。

检查动物存活时间和肿瘤生长减少的速率/速度。研究表明,EP 或 SP 及其组合 (EP + SP) 均能够在治疗后第 3 天诱导肿瘤体积减小。在 SP 之前使用 EP 可以显着降低惯性空化剂量 (ICD) 的值,这是诱导肿瘤完全减少和延长动物存活所必需的。

对超声 (US) 侧向散射信号和 B 扫描成像的分析表明在我们的实验条件下发生了惯性空化。ICD 与相应未恢复小鼠的存活时间的强 (R 2 = 0.88; p < 0.0001) 相关性表明在体内实践 中可以选择剂量控制和空化活动标准化。

更新日期:2022-05-12
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