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电穿孔增强 GB-10 介导的体内 BNCT 治疗口腔癌的疗效。

Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer.

机构信息

Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Pabellón I, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2270, Buenos Aires C1425FQD, Argentina.

出版信息

Cells. 2023 Apr 25;12(9):1241. doi: 10.3390/cells12091241.

DOI:10.3390/cells12091241
PMID:37174642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10177359/
Abstract

Boron neutron capture therapy (BNCT) combines preferential tumor uptake of B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) as the boron carrier in a hamster cheek pouch oral cancer model. The aim of the present study was to evaluate if EP could improve tumor control without enhancing the radiotoxicity of BNCT in vivo mediated by GB-10 with EP 10 min after GB-10 administration. Following cancerization, tumor-bearing hamster cheek pouches were treated with GB-10/BNCT or GB-10/BNCT + EP. Irradiations were carried out at the RA-3 Reactor. The tumor response and degree of mucositis in precancerous tissue surrounding tumors were evaluated for one month post-BNCT. The overall tumor response (partial remission (PR) + complete remission (CR)) increased significantly for protocol GB-10/BNCT + EP (92%) vs. GB-10/BNCT (48%). A statistically significant increase in the CR was observed for protocol GB-10/BNCT + EP (46%) vs. GB-10/BNCT (6%). For both protocols, the radiotoxicity (mucositis) was reversible and slight/moderate. Based on these results, we concluded that electroporation improved the therapeutic efficacy of GB-10/BNCT in vivo in the hamster cheek pouch oral cancer model without increasing the radiotoxicity.

摘要

硼中子俘获治疗（BNCT）结合了肿瘤对 B 化合物的优先摄取和中子照射。电穿孔诱导细胞膜通透性增加。我们之前已经证明了通过电穿孔（EP）和十氢-癸硼烷（GB-10）作为硼载体优化硼的生物分布和微分布，在仓鼠颊囊口腔癌模型中。本研究的目的是评估 EP 是否可以在体内不增加由 EP 介导的 GB-10 的放射毒性的情况下改善肿瘤控制，GB-10 在给药后 10 分钟进行 EP。在癌变后，用 GB-10/BNCT 或 GB-10/BNCT+EP 治疗携带肿瘤的仓鼠颊囊。辐照在 RA-3 反应堆中进行。在 BNCT 后一个月评估癌前组织中肿瘤反应和粘膜炎的程度。与 GB-10/BNCT 相比，方案 GB-10/BNCT+EP 的总肿瘤反应（部分缓解（PR）+完全缓解（CR））显著增加（92%对 48%）。方案 GB-10/BNCT+EP 的 CR 增加有统计学意义（46%对 6%）。对于这两种方案，放射毒性（粘膜炎）是可逆的，轻微/中度。基于这些结果，我们得出结论，电穿孔在不增加放射毒性的情况下，提高了仓鼠颊囊口腔癌模型中 GB-10/BNCT 的体内治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/5354362053b5/cells-12-01241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/142363f55d77/cells-12-01241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/439ba2174a8f/cells-12-01241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/5354362053b5/cells-12-01241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/142363f55d77/cells-12-01241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/439ba2174a8f/cells-12-01241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/122a/10177359/5354362053b5/cells-12-01241-g003.jpg

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