Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima, 739-8527, Japan.
Program of Applied Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima, 739-8527, Japan.
Biochem Biophys Res Commun. 2021 Jun 25;559:210-216. doi: 10.1016/j.bbrc.2021.04.037. Epub 2021 May 3.
In cancer therapeutics, boron neutron capture therapy (BNCT) requires a platform for selective and efficient B delivery into tumor tissues for a successful treatment. However, the use of carborane, a promising candidate with high boron content and biostability, has significant limitations in the biomedical field due to its poor water-solubility and tumor-selectivity. To overcome these hurdles, we present in this study a fluorescent nano complex, combining fluorescent carborane and sodium hyaluronate for high boron concentration and tumor-selectivity. Tumor cells actively internalized the complex through binding hyaluronan to CD44, overexpressed on the tumor cell surface. Furthermore, the subcellular distribution of this complex could also be detected due to its fluorescent properties. Moreover, after thermal neutron irradiations, the complex produced excellent cytotoxicity, equal to or greater than that of the clinically-used BPA-fructose. Therefore, this novel complex could be potentially more suitable for BNCT than the boron agent.
在癌症治疗中，硼中子俘获治疗（BNCT）需要一个平台，将硼选择性且有效地递送到肿瘤组织中，以实现成功的治疗。然而，由于 carborane（一种具有高硼含量和生物稳定性的有前途的候选物）水溶性差和肿瘤选择性差，在生物医药领域的应用受到了显著限制。为了克服这些障碍，我们在这项研究中提出了一种荧光纳米复合物，将荧光 carborane 与透明质酸钠结合，以实现高硼浓度和肿瘤选择性。肿瘤细胞通过与肿瘤细胞表面过度表达的 CD44 结合，主动内化该复合物。此外，由于其荧光特性，还可以检测到该复合物的亚细胞分布。此外，经过热中子辐照后，该复合物产生了优异的细胞毒性，与临床使用的 BPA-果糖相当或更高。因此，与硼剂相比，这种新型复合物可能更适合 BNCT。
