Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation for BNCT in a Rat Melanoma Model.
Boron Delivery to Brain Cells via Cerebrospinal Fluid (CSF) Circulation for BNCT in a Rat Melanoma Model.
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DOI：
10.3390/biology11030397
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发表时间：
2022-03-03
期刊：
影响因子：
4.2
通讯作者：
Murata I
中科院分区：
文献类型：
--
作者：
Kusaka S;Morizane Y;Tokumaru Y;Tamaki S;Maemunah IR;Akiyama Y;Sato F;Murata I
血脑屏障（BBB）由脑毛细血管内皮形成，可阻止几乎所有治疗药物到达大脑。直到最近，BBB 在脑肿瘤治疗中的重要性才被认识到，包括硼中子捕获疗法 (BNCT)，尽管它会影响治疗脑肿瘤时的治疗效果。最近，一些绕过血脑屏障的药物输送系统被开发用于脑肿瘤治疗，我们实验室正在开发一种利用脑脊液（CSF）循环将硼输送到脑细胞的系统，我们称之为“硼CSF给药方法”。在这项研究中，我们用脑肿瘤模型大鼠进行了实验，以证明脑脊液给药方法对于 BNCT 的有效性。结果，我们发现使用脑脊液给药方法注射的硼在肿瘤细胞中积累到高水平，并且具有高T/N比。此外，硼药物所需的剂量远低于静脉注射（IV）给药方法中达到同等效果的剂量。这种方法使临床医生可以向患者注射较低的药物剂量，从而减少过量药物的潜在副作用并降低其成本。我们希望我们的发现能够激发更多关于将硼输送到脑肿瘤以进行 BNCT 的研究。最近，利用脑脊液（CSF）循环已被越来越多地认为是解决脑肿瘤药物输送挑战的可行策略。硼中子俘获疗法（BNCT）还面临着开发有效的硼输送系统（尤其是脑肿瘤）相关的挑战。我们的实验室一直在开发一种利用脑脊液将硼输送到脑细胞的系统，我们称之为“硼脑脊液给药方法”。在我们之前的研究中，我们发现通过脑脊液给药方法，硼可以以少量L-对硼苯丙氨酸（BPA）的形式有效地输送到正常大鼠的脑细胞。在此描述的研究中，我们对脑肿瘤模型大鼠进行了实验，以证明 CSF 给药方法对于 BNCT 的有用性。我们首先研究了正常大鼠侧脑室注射 BPA 后每 60 分钟脑细胞的硼浓度。其次，我们测量并比较了通过脑脊液施用方法或静脉内（IV）施用方法施用硼后黑色素瘤模型大鼠中的硼浓度，并估计了T/N比。我们的结果表明，通过 CSF 给药方法注射的硼可以从正常细胞中快速排出，与 IV 给药相比，导致较高的 T/N 比。此外，脑脊液给药方法会导致肿瘤细胞中硼的大量积累。总之，我们发现，与 IV 给药方法相比，使用我们开发的 CSF 给药方法可以更选择性地将硼递送至脑肿瘤。
The blood–brain barrier (BBB) is formed by the brain capillary endothelium and prevents almost all therapeutic agents from reaching the brain. The importance of the BBB in brain tumor treatments has not been recognized until recently, including in the case of boron neutron capture therapy (BNCT), although it affects therapeutic efficacy when treating brain tumors. Recently, some drug delivery systems to bypass the BBB have been developed for brain tumor therapy, and our laboratory has been developing a system for boron delivery to brain cells using cerebrospinal fluid (CSF) circulation, which we call the “boron CSF administration method”. In this study, we carried out experiments with brain tumor model rats to demonstrate the usefulness of the CSF administration method for BNCT. As a result, we found that boron injected using the CSF administration method accumulates to high levels in tumor cells, with a high T/N ratio. In addition, the dose required for the boron drug was much lower than that used in the intravenous (IV) administration method for equivalent effects. This approach makes it possible for clinicians to inject a lower drug dose into patient, thus reducing the potential side effects of excessive amounts of the drug and decreasing its cost. We hope our findings will inspire additional studies on boron delivery to brain tumors for BNCT. Recently, exploitation of cerebrospinal fluid (CSF) circulation has become increasingly recognized as a feasible strategy to solve the challenges involved in drug delivery for treating brain tumors. Boron neutron capture therapy (BNCT) also faces challenges associated with the development of an efficient delivery system for boron, especially to brain tumors. Our laboratory has been developing a system for boron delivery to brain cells using CSF, which we call the “boron CSF administration method”. In our previous study, we found that boron was efficiently delivered to the brain cells of normal rats in the form of small amounts of L-p-boronophenylalanine (BPA) using the CSF administration method. In the study described here, we carried out experiments with brain tumor model rats to demonstrate the usefulness of the CSF administration method for BNCT. We first investigated the boron concentration of the brain cells every 60 min after BPA administration into the lateral ventricle of normal rats. Second, we measured and compared the boron concentration in the melanoma model rats after administering boron via either the CSF administration method or the intravenous (IV) administration method, with estimation of the T/N ratio. Our results revealed that boron injected by the CSF administration method was excreted quickly from normal cells, resulting in a high T/N ratio compared to that of IV administration. In addition, the CSF administration method resulted in high boron accumulation in tumor cells. In conclusion, we found that using our developed CSF administration method results in more selective delivery of boron to the brain tumor compared with the IV administration method.
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影响因子：
4.2
作者：
Fukuo Y;Hattori Y;Kawabata S;Kashiwagi H;Kanemitsu T;Takeuchi K;Futamura G;Hiramatsu R;Watanabe T;Hu N;Takata T;Tanaka H;Suzuki M;Miyatake SI;Kirihata M;Wanibuchi M
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0.2
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影响因子：
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影响因子：
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