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Hyaluronan as Carrier of Carboranes for Tumor Targeting in Boron Neutron Capture Therapy

机译：透明质酸作为硼烷的载体，用于硼中子俘获治疗中的靶向肿瘤。

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Boron neutron capture therapy(BNCT)represents a promising approach for tumor therapy.A critical requirement for BNCT is tumor targeting,a goal that is currently addressed with the development of low and high molecular weight agents capable of interacting with receptors expressed by cancer cells.Here,we describe a new bioconjugate(HApCB)composed by n-propyl carborane linked to hyaluronan(HA)via an ester linkage for a degree of substitution of approximately 30%,leading to a water-soluble derivative.The structure and main physicochemical characteristics of the new HA derivative were determined by means of Fourier transform infrared,fluorescence,and 1H,13C,and 10B NMR analysis and are herein reported in detail.As HA is recognized by the CD44 antigen,densely populating the surface of many tumor cells,HApCB is expected to deliver boron atoms from the locally released carborane cages directly to target cells for antitumor application in BNCT.In vitro biological experiments showed that HApCB was not toxic for a variety of human tumor cells of different histotypes,specifically interacted with CD44 as the native unconjugated HA,and underwent uptake by tumor cells,leading to accumulation of amounts of boron atoms largely exceeding those required for a successful BNCT approach.Thus,HApCB may be regarded as a promising new BNCT agent for specific targeting of cancer cells overexpressing the CD44 receptor.
机译：硼中子捕获疗法（BNCT）代表了一种有前途的肿瘤治疗方法。BNCT的一项关键要求是靶向肿瘤，这一目标目前正在开发能够与癌细胞表达的受体相互作用的低分子量和高分子量药物。在这里，我们描述了一种新的生物共轭物（HApCB），它由正丙基甲硼烷通过酯键与透明质酸（HA）相连，取代度约为30％，从而形成水溶性衍生物。其结构和主要理化特性通过傅立叶变换红外，荧光，1H，13C和10B NMR分析确定了新的HA衍生物的含量，并在本文中进行了详细报道。由于HA被CD44抗原识别，致密地分布在许多肿瘤细胞的表面， HApCB有望将硼原子从局部释放的碳硼烷笼中直接传递至靶细胞，以用于BNCT的抗肿瘤应用。由于对多种不同组织类型的人类肿瘤细胞无毒，因此与CD44作为天然的未结合HA特异性相互作用，并被肿瘤细胞吸收，导致积累的硼原子数量大大超过了成功BNCT方法所需的数量。 ，HApCB可以被认为是针对过表达CD44受体的癌细胞的特异性靶向的有希望的新BNCT剂。

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