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碘纳米颗粒放疗对裸鼠脑内生长的人乳腺癌的疗效。

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice.

机构信息

Nanoprobes, Inc., 95 Horseblock Rd., Unit 1, Yaphank, NY, 11980, USA.

Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT, 06030, USA.

出版信息

Sci Rep. 2020 Sep 24;10(1):15627. doi: 10.1038/s41598-020-72268-0.

Abstract

About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3-4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days.

摘要

大约 30%的乳腺癌会转移到大脑;那些广泛传播的乳腺癌通常在 3-4 个月内致命,即使采用包括手术、药物和放射治疗在内的最佳现有治疗方法也是如此。为了解决这一严峻局面,我们开发了碘纳米颗粒(INP),这些颗粒在静脉注射(IV)后可靶向脑部肿瘤。然后,碘在放射治疗(RT)期间吸收 X 射线,产生自由基并造成局部肿瘤损伤,有效地提高了肿瘤部位的局部 RT 剂量。采用在免疫缺陷裸鼠大脑中生长的侵袭性很强的三阴性乳腺癌(TNBC,MDA-MB-231 细胞)对疗效进行了测试。INP 的 IV 剂量(7g 碘/公斤体重)耐受良好且无毒,肿瘤显示出碘高度浓聚的边缘,肿瘤的平均碘重量摄取率为 2.9%,摄取峰值为 4.5%。这被计算为提供约 5.5 的剂量增强因子(峰值为 8.0),这是迄今为止报告的任何辐射增强剂中最高的。单独接受 RT(15Gy,单次剂量)的所有动物在 72 天内死亡;INP 预处理可延长缓解期,40%的小鼠存活 150 天,30%的小鼠存活时间超过 280 天。

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