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壳聚糖-萘酰亚胺探针双通道识别细胞中HClO和H2S及其在光动力治疗中的应用。

Chitosan-naphthalimide probes for dual channel recognition of HClO and H2S in cells and their application in photodynamic therapy.

发表日期:2024 Oct 17
作者: Bo Zhao, Jun Liu, Caiqiong Zhu, Xinjian Cheng
来源: Int J Biol Macromol

摘要:

生物成像与光动力疗法(PDT)相结合来完成治疗诊断在癌症治疗中具有广阔的前景。这项工作研究了三种壳聚糖-萘二甲酰亚胺探针。首先合成4-(5-溴噻吩-2-基)-1,8-萘二甲酸酐,然后与壳聚糖反应得到大分子(CS-N-Br)。将识别基团硫代吗啉或其衍生物引入CS-N-Br中,最终得到纳米探针(CS-N-ML、CS-N-BSZ、CS-N-FSQ)。研究表明CS-N-ML和CS-N-FSQ具有高选择性,可以特异性识别HClO和H2S。 CS-N-ML 和 CS-N-FSQ 还可以对细胞中的 HClO 和 H2S 进行外源和内源共聚焦成像。 CS-N-ML 靶向溶酶体位置的能力表明它可以充当溶酶体特异性探针。研究发现探针通过 I 型机制产生超氧阴离子 (O2•-)。这一发现赋予探针即使在缺氧条件下也具有高光敏活性。缀合系统的程度与探针的光敏度之间存在正相关,表明增强的缀合导致光敏度增加。在光照射下,探针在 HeLa 细胞内产生 ROS。这些结果表明这些探针可以实现与 HClO 和 H2S 水平异常相关的疾病的治疗诊断。版权所有 © 2024。由 Elsevier B.V. 出版。
The combination of bio-imaging with photodynamic therapy (PDT) to accomplish theranostics is promising in cancer treatment. Three chitosan-naphthalimide probes were studied in this work. 4-(5-Bromothiophen-2-yl)-1,8-naphthalic anhydride was first synthesized, and then reacted with chitosan to obtain the macromolecules (CS-N-Br). The recognition group thiomorpholine or its derivatives were introduced into CS-N-Br to obtain nano-probes (CS-N-ML, CS-N-BSZ, CS-N-FSQ) eventually. The studies revealed that CS-N-ML and CS-N-FSQ exhibit high selectivity and can specifically recognize HClO and H2S. CS-N-ML and CS-N-FSQ can perform exogenous and endogenous confocal imaging of HClO and H2S in cells also. CS-N-ML's ability to target lysosomes positions indicated it could act as a lysosome-specific probe. It was discovered that the probes generate superoxide anions (O2•-) via a Type I mechanism. This discovery endows the probes with high photosensitizing activity even under hypoxic conditions. There is a positive correlation between the extent of the conjugated system and the photosensitivity of the probes, indicating that an enhanced conjugation leads to increased photosensitivity. Upon light irradiation, the probes generate ROS within HeLa cells. These results suggested that these probes can achieve theranostics for diseases associated with abnormal levels of HClO and H2S.Copyright © 2024. Published by Elsevier B.V.