Zhang Mingjie, Gao Shanghui, Yang Kai, Jiang Benchun, Xu Wei, Islam Waliul, Koike Shinnosuke, Kinoshita Yusei, Nakayama Hiroto, Zhou Jianrong, Yokomizo Kazumi, Fang Jun
Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Pharmaceutics. 2025 Jun 4;17(6):738. doi: 10.3390/pharmaceutics17060738.
: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene-maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which exhibited tumor-targeted distribution via the enhanced permeability and retention (EPR) effect. Building upon this approach, in this study, we designed and synthesized a series of SMA-based polymeric probes for BNCT and evaluated their biological activities, with a particular focus on tumor-targeting properties. : Two SMA-based BNCT nanoprobes, SMA-glucosamine conjugated Borax (SG@B) and SMA-conjugated aminophenylboronic acid encapsulating tavaborole (S-APB@TB), were designed and synthesized. The boron content in the conjugates was quantified using inductively coupled plasma mass spectrometry (ICP-MS), while particle sizes were measured via dynamic light scattering (DLS). In vitro cytotoxicity was assessed using the MTT assay in mouse colon cancer C26 cells. The tissue distribution of the conjugates was analyzed in a mouse sarcoma S180 solid tumor model using ICP-MS. : Both SG@B and S-APB@TB formed nanoformulations with average particle sizes of 137 nm and 99 nm, respectively. The boron content of SG@B was 2%, whereas S-APB@TB exhibited a significantly higher boron content of 14.4%. Both conjugates demonstrated dose-dependent cytotoxicity against C26 cells, even in the absence of neutron irradiation. Notably, tissue distribution analysis following intravenous injection revealed higher boron concentrations in plasma and tumor tissues compared to most normal tissues, with S-APB@TB showing particularly favorable tumor accumulation. : These findings highlight the tumor-targeting potential of SMA-based BNCT nanoprobes. Further investigations are warranted to advance their clinical development as BNCT agents.
硼中子俘获疗法（BNCT）是一种很有前景的、侵入性较小的抗癌治疗方法。然而，开发有效的硼基试剂（BNCT探针）仍然是一个关键且具有挑战性的问题。此前，我们开发了一种与葡糖胺共轭的苯乙烯-马来酸（SMA）共聚物，其包裹硼酸，通过增强渗透和滞留（EPR）效应表现出肿瘤靶向分布。基于此方法，在本研究中，我们设计并合成了一系列用于BNCT的基于SMA的聚合物探针，并评估了它们的生物学活性，特别关注肿瘤靶向特性。
设计并合成了两种基于SMA的BNCT纳米探针，即与硼砂共轭的SMA-葡糖胺（SG@B）和包裹他伏硼罗的SMA-共轭氨基苯硼酸（S-APB@TB）。使用电感耦合等离子体质谱（ICP-MS）对共轭物中的硼含量进行定量，同时通过动态光散射（DLS）测量粒径。使用MTT法在小鼠结肠癌C26细胞中评估体外细胞毒性。使用ICP-MS在小鼠肉瘤S180实体瘤模型中分析共轭物的组织分布。
SG@B和S-APB@TB均形成了纳米制剂，平均粒径分别为137nm和99nm。SG@B的硼含量为2%，而S-APB@TB的硼含量显著更高，为14.4%。即使在没有中子照射的情况下，两种共轭物对C26细胞均表现出剂量依赖性细胞毒性。值得注意的是，静脉注射后的组织分布分析显示，与大多数正常组织相比，血浆和肿瘤组织中的硼浓度更高，S-APB@TB表现出特别有利的肿瘤蓄积。
这些发现突出了基于SMA的BNCT纳米探针的肿瘤靶向潜力。有必要进一步研究以推动它们作为BNCT试剂的临床开发。
