Institute of Chemical Biology and Fundamental Medicine, SB RAS, 630090 Novosibirsk, Russia.
Faculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Molecules. 2021 Oct 29;26(21):6537. doi: 10.3390/molecules26216537.
Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)-a carrier protein with a long plasma half-life-is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-'click' chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro--dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 μM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro--dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imaging-guided boron neutron capture therapy.
硼中子俘获治疗是一种独特的辅助癌症治疗方法，适用于包括恶性胶质瘤在内的各种恶性肿瘤。硼化合物与人体血清白蛋白（HSA）的结合——一种具有长血浆半衰期的载体蛋白——有望延长硼化合物的全身循环，并增加其在人神经胶质瘤细胞中的积累。我们报告了荧光标记的同型半胱酰胺缀合的人血清白蛋白的合成及其在硫醇“点击”化学中的应用，以制备新型的多模态硼化白蛋白基治疗剂，这些治疗剂可以在肿瘤细胞中积累。这项工作的新颖之处在于开发了用于成像引导硼中子俘获治疗联合的白蛋白缀合物的合成方法。在这里，我们建议使用三氟乙酰丙酮作为抗癌治疗结构的一部分：大约 5.4 个三氟乙酰丙酮分子与每个白蛋白结合。三氟乙酰丙酮除了作为化疗药物的有益特性外，还是一种很有前途的磁共振成像剂。双模态 HSA 与十一氢-十二硼酸盐的缀合仅在没有辐照的情况下（~30 μM 硼化白蛋白）略微降低人神经胶质瘤细胞系的活力，但允许在中能中子通量下进行中子俘获并降低肿瘤细胞的存活率。在获得的 HSA 缀合物中同时存在十一氢-十二硼酸盐和标记的氨基酸残基（荧光染料和氟原子），这使其成为组合成像引导硼中子俘获治疗的有前途的候选物。
