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Discovery of an Amino Acid-Modified Near-Infrared Aza-BODIPY Photosensitizer as an Immune Initiator for Potent Photodynamic Therapy in Melanoma
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-02-12 , DOI: 10.1021/acs.jmedchem.1c02154 Zhiliang Yu 1 , Hong Wang 2 , Zhongjian Chen 1 , Xiaochun Dong 3 , Weili Zhao 3, 4 , Yuling Shi 1 , Quangang Zhu 1
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-02-12 , DOI: 10.1021/acs.jmedchem.1c02154 Zhiliang Yu 1 , Hong Wang 2 , Zhongjian Chen 1 , Xiaochun Dong 3 , Weili Zhao 3, 4 , Yuling Shi 1 , Quangang Zhu 1
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The discovery of novel photosensitizers with potent phototoxicity and desirable water solubility is an urgent task for photodynamic therapy. Herein, a series of amino acid-modified aza-BODIPY photosensitizers were synthesized and evaluated. These new PSs exhibited enhanced aqueous solubility, increased 1O2 generation efficiency, and an improved photo-dark toxicity ratio. Aspartic acid-modified PS of 1a, which possessed intense NIR absorption and high 1O2 quantum yield, demonstrated the most potent efficacy toward the investigated tumor cell lines without using an emulsifier. Subcellular localization, cell-based ROS production, and cell death pathway of 1a were studied. In vivo fluorescence imaging and ex vivo organ distribution assays manifested that 1a possessed reasonable distribution and clearance. In vivo PDT studies indicated that 1a revealed advantages over Ce6 and our previously optimized PS of BDP-4. It not only afforded an excellent PDT effect with a low drug dose under only single-time photoirradiation but also induced an antitumor immunological response.
中文翻译：
发现一种氨基酸修饰的近红外 Aza-BODIPY 光敏剂作为有效光动力治疗黑色素瘤的免疫引发剂
发现具有强光毒性和理想水溶性的新型光敏剂是光动力治疗的一项紧迫任务。本文合成并评价了一系列氨基酸修饰的aza-BODIPY光敏剂。这些新的 PS 表现出增强的水溶性、增加的1 O 2生成效率和改善的光暗毒性比。天冬氨酸修饰的1a的 PS具有强烈的 NIR 吸收和高1 O 2量子产率，在不使用乳化剂的情况下对所研究的肿瘤细胞系表现出最有效的功效。研究了1a的亚细胞定位、基于细胞的 ROS 产生和细胞死亡途径。体内荧光成像和离体器官分布测定表明1a具有合理的分布和清除。体内PDT 研究表明，1a显示出优于Ce6和我们之前优化的BDP-4 PS 的优势。它不仅在单次光照射下以低药物剂量提供了优异的PDT效果，而且还诱导了抗肿瘤免疫反应。
更新日期：2022-02-12
中文翻译：
发现一种氨基酸修饰的近红外 Aza-BODIPY 光敏剂作为有效光动力治疗黑色素瘤的免疫引发剂
发现具有强光毒性和理想水溶性的新型光敏剂是光动力治疗的一项紧迫任务。本文合成并评价了一系列氨基酸修饰的aza-BODIPY光敏剂。这些新的 PS 表现出增强的水溶性、增加的1 O 2生成效率和改善的光暗毒性比。天冬氨酸修饰的1a的 PS具有强烈的 NIR 吸收和高1 O 2量子产率，在不使用乳化剂的情况下对所研究的肿瘤细胞系表现出最有效的功效。研究了1a的亚细胞定位、基于细胞的 ROS 产生和细胞死亡途径。体内荧光成像和离体器官分布测定表明1a具有合理的分布和清除。体内PDT 研究表明，1a显示出优于Ce6和我们之前优化的BDP-4 PS 的优势。它不仅在单次光照射下以低药物剂量提供了优异的PDT效果，而且还诱导了抗肿瘤免疫反应。
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