水溶性苯並咪唑衍生物之近紅外光響應材料的設計、合成與生醫應用

Abstract

本研究成功開發一系列水溶性苯並咪唑衍生物之近紅外光響應材料，可作為生物螢光顯影探針 (fluorescent probe) 及光照療法 (phototherapy) 之光響應材料。 本研究之有機小分子材料設計採用不對稱的予體-受體-受體 (donor-acceptor-acceptor’, D-A-A’) 結構，電子予體 (D) 選用高電子密度的二甲氧基二苯胺 (bis(4-methoxyphenyl)amine)，搭配不同π架橋連接核心受體 (A) 萘并噻二唑 (naphthothiadiazole, NBT)，另一受體 (A’) 選用具有高度生物相容性的離子化苯並咪唑 (benzimidazole) 衍生物，開發出 PA-NBTI+、ThPA-NBTI+ 及 BTPA-NBTI+。此系列分子具陽離子結構，有效提高分子水溶性，使其得以直接進入生物體應用，亦具粒線體靶向能力。經由光物理性質分析，推測 PA-NBTI+ 與 BTPA-NBTI+ 之激發態能量多以非輻射形式散失，因此後續將以光聲成像、光熱療法與光動力療法為主要應用方向；另外 ThPA-NBTI+ 放光範圍涵蓋 NIR-I 並進入 NIR-II 範圍，具備螢光顯影探針之應用潛力。經由細胞實驗結果顯示，三者皆展現良好的生物相容性，且與粒線體具高度共定位效果，後續將執行螢光顯影、光熱與光動力療法效能評估。

A series of water-soluble benzimidazole derivatives were synthesized and characterized as near-infrared (NIR) responsive materials for bioimaging and phototherapy. These asymmetric donor-acceptor-acceptor' (D-A-A') small organic molecules were designed by incorporating naphthothiadiazole (NBT) as an electron-accepting core (A), along with a cationic benzimidazole-derived acceptor (A') with excellent biocompatibility. Bis(4-methoxyphenyl)amine was employed as a strong electron donor (D) to construct the push–pull electronic structure. The donor and acceptor moieties were linked via different π-bridges to afford three positively charged molecules：PA-NBTI+, ThPA-NBTI+, and BTPA-NBTI+. These cationic molecules exhibit highly water solubility, enabling direct biological application without requiring encapsulation by amphiphilic polymers. Additionly, their cationic nature promotes selective mitochondrial targeting. Photophysical characterization revealed that PA-NBTI+ and BTPA-NBTI+ primarily undergo non-radiative decay from their excited states, suggesting their potential for photoacoustic imaging (PAI), photothermal therapy (PTT), and photodynamic therapy (PDT). In contrast, ThPA-NBTI+ exhibited broad emission spanning the NIR-I region and extending into the NIR-II window, highlighting its promise for fluorescence imaging applications. Based on cellular experiments, all three compounds showed excellent biocompatibility and strong mitochondrial colocalization. Their potential applications in fluorescence imaging, PTT, and PDT will be further investigated.