Kondo Naoya, Takada Shinya, Hagimori Masayori, Temma Takashi
Department of Biofunctional Analysis, Graduate School of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki 569-1094, Osaka, Japan.
Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyubancho, Nishinomiya 663-8179, Hyogo, Japan.
Cancers (Basel). 2023 Mar 20;15(6):1862. doi: 10.3390/cancers15061862.
Boron neutron capture therapy (BNCT) is an attractive approach to treating cancers. Currently, only one B-labeled boronoagent (Borofalan, BPA) has been approved for clinical BNCT in Japan, and methods for predicting and measuring BNCT efficacy must be established to support the development of next-generation B-boronoagents. Fluorescence sensors targeting boronic acids can achieve this because the amount and localization of B in tumor tissues directly determine BNCT efficacy; however, current sensors are nonoptimal given their slow reaction rate and weak fluorescence (quantum yield < 0.1). Herein, we designed and synthesized a novel small molecular-weight fluorescence sensor, BITQ, targeting boronic acids. In vitro qualitative and quantitative properties of BITQ were assessed using a fluorophotometer and a fluorescence microscope together with BPA quantification in blood samples. BITQ exhibited significant quantitative and selective fluorescence after reacting with BPA (post-to-pre-fluorescence ratio = 5.6; quantum yield = 0.53); the fluorescence plateaued within 1 min after BPA mixing, enabling the visualization of intracellular BPA distribution. Furthermore, BITQ quantified the BPA concentration in mouse blood with reliability comparable with that of current methods. This study identifies BITQ as a versatile fluorescence sensor for analyzing boronic acid agents. BITQ will contribute to B-boronoagent development and promote research in BNCT.
硼中子俘获疗法（BNCT）是一种颇具吸引力的癌症治疗方法。目前，在日本仅有一种硼标记的硼药（硼苯丙氨酸，BPA）被批准用于临床BNCT，因此必须建立预测和测量BNCT疗效的方法，以支持下一代硼药的研发。靶向硼酸的荧光传感器能够实现这一目标，因为肿瘤组织中硼的含量和定位直接决定了BNCT的疗效；然而，目前的传感器反应速率慢且荧光较弱（量子产率<0.1），并不理想。在此，我们设计并合成了一种新型的小分子荧光传感器BITQ，用于靶向硼酸。使用荧光光度计和荧光显微镜评估了BITQ的体外定性和定量特性，并对血样中的BPA进行了定量分析。BITQ与BPA反应后表现出显著的定量和选择性荧光（荧光后与荧光前的比率=5.6；量子产率=0.53）；与BPA混合后1分钟内荧光达到平稳，能够实现细胞内BPA分布的可视化。此外，BITQ对小鼠血液中BPA浓度的定量分析具有与现有方法相当的可靠性。本研究确定BITQ是一种用于分析硼酸制剂的通用荧光传感器。BITQ将有助于硼药的研发，并推动BNCT的研究。
