Li Jun-Hui, You Pei-Dan, Lu Fei, Huang Jun-Tao, Fu Jia-Luo, Tang Hao-Yun, Zhou Chun-Qiong
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
J Photochem Photobiol B. 2023 Mar;240:112653. doi: 10.1016/j.jphotobiol.2023.112653. Epub 2023 Jan 25.
On the base of the zwiterionic dibenzothiazole squaraine SQ, five cationic aromatics sulfonamide substituted dibenzothiazole squaraines SQ-D1 ∼ 5 have been designed and synthesized. Through the formation of the cationic compound, a higher rigid structure and the addition of the strong electron-withdrawing group (-CN), an ideal photosensitizer SQ-D2 has been gotten. In all the sulfonaminosquaraines, compound SQ-D2 exhibited the highest ROS generation efficacy and photostability. It also showed the highest photo-cytotoxicity (IC = 0.25 ± 0.08 μM), very low dark-cytotoxicity and the excellent cell uptake. In animal study, it not only showed the effective tumor retention and the easy removal from the body, but also exhibited the effective PDT efficacy at low drug dose (0.15 mg/kg) and the good biocompatibility. Furthermore, photosensitizer SQ-D2 as a single component exhibited greater potential than clinically approved photosensitizer m-THPC and some nanomaterials with photosensitizers in PDT therapy towards human breast cancer. This work provides a new perspective to develop the ideal photosensitizer of the squaraine dyes.
基于两性离子二苯并噻唑方酸菁SQ，设计并合成了5种阳离子芳族磺酰胺取代的二苯并噻唑方酸菁SQ-D1∼5。通过形成阳离子化合物、获得更高的刚性结构以及引入强吸电子基团（-CN），得到了理想的光敏剂SQ-D2。在所有磺酰胺基方酸菁中，化合物SQ-D2表现出最高的活性氧生成效率和光稳定性。它还表现出最高的光细胞毒性（IC = 0.25±0.08 μM）、极低的暗细胞毒性和优异的细胞摄取能力。在动物研究中，它不仅显示出有效的肿瘤滞留和易于从体内清除，还在低药物剂量（0.15 mg/kg）下表现出有效的光动力治疗效果和良好的生物相容性。此外，光敏剂SQ-D2作为单一成分在光动力治疗中对人乳腺癌表现出比临床批准的光敏剂m-THPC和一些含光敏剂的纳米材料更大的潜力。这项工作为开发理想的方酸菁染料光敏剂提供了新的视角。
