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The mechanism of novel potential porphyrin photosensitizer mediated phototherapy in SH-SY5Y cell lines and the effect of TMeQ[6] self-assembly in therapy
Journal of Porphyrins and Phthalocyanines ( IF 1.5 ) Pub Date : 2023-07-01 , DOI: 10.1142/s1088424623501092
Zhouxia Lu 1 , Yan Guo 2 , Conghui Wang 1 , Xuelian Luo 1 , Song Xiao 1
Affiliation  

Porphyrin PSs, possessing high photosensitivity and stability, have widespread use in phototherapy. Furthermore, the use of Q[n]s as a carrier for PSs has contributed to enhancing the efficacy of photodynamic therapy. In the present study, we synthesized 2TMeQ[6]-TPPPA self-assembled compounds, comprising TMeQ[6] and 5, 10, 15, 20-tetra (4-pyridyl, N-propyl ammonia) porphyrin derivatives (TPPPA) (in a 2:1 ratio), to investigate their capacity to generate reactive oxygen species (ROS) and their effect of self-assembly with TMeQ[6] on the efficacy of human neuroblastoma cell line (SH-SY5Y). Our results demonstrate that both TPPPA and 2TMeQ[6]-TPPPA generate substantial amounts of ROS under laser irradiation, which is directly proportional to the duration of illumination. Furthermore, both compounds exhibited significant cytotoxic effects on SH-SY5Y cells, as demonstrated by the MTT assay. Western blotting revealed a marked increase in the expression of Cleaved caspase-3, Cleaved caspase-9, and Bax, and a decrease in the expression of Bcl-2, confirming that caspase-dependent apoptosis is involved in SH-SY5Y cell death induced by TPPPA photodynamic therapy. ROS overproduction plays a crucial role in this process, and NAC preconditioning was shown to reduce cytotoxicity and inhibit pro-apoptotic protein molecules. However, 2TMeQ[6]-TPPPA was less effective than TPPPA in terms of ROS production capacity and toxicity to SH-SY5Y cells after self-assembling with TMeQ[6]. In conclusion, our study explored that TPPPA can induce ROS overproduction leading to apoptosis, and its mediated photodynamic therapy is a highly effective treatment option for SH-SY5Y cells. After self-assembling with TMeQ[6], TPPPA retains its apoptotic pathway-inducing characteristics and acts as a carrier, but this is not conducive to the photodynamic enhancement of TPPPA.



中文翻译:

新型潜在卟啉光敏剂介导的SH-SY5Y细胞光疗机制及TMeQ[6]自组装在治疗中的作用

卟啉PSs具有高光敏性和稳定性,在光治疗中有着广泛的应用。此外,使用Q[n]s作为PSs的载体有助于提高光动力疗法的功效。在本研究中,我们合成了2TMeQ[6]-TPPPA自组装化合物,包括TMeQ[6]和5,10,15,20-四(4-吡啶基,N-丙基氨)卟啉衍生物(TPPPA)(在2:1 的比例),研究它们产生活性氧(ROS)的能力以及它们与 TMeQ[6] 自组装对人神经母细胞瘤细胞系(SH-SY5Y)功效的影响。我们的结果表明,TPPPA 和 2TMeQ[6]-TPPPA 在激光照射下都会产生大量的 ROS,这与照射时间成正比。此外,MTT 测定表明,这两种化合物对 SH-SY5Y 细胞均表现出显着的细胞毒性作用。Western blotting结果显示Cleaved caspase-3、Cleaved caspase-9和Bax的表达显着增加,而Bcl-2的表达减少,证实caspase依赖性细胞凋亡参与了由Cleaved caspase诱导的SH-SY5Y细胞死亡。 TPPPA 光动力疗法。ROS 过量产生在此过程中起着至关重要的作用,NAC 预处理被证明可以降低细胞毒性并抑制促凋亡蛋白分子。然而,与TMeQ[6]自组装后,2TMeQ[6]-TPPPA在ROS产生能力和对SH-SY5Y细胞的毒性方面不如TPPPA有效。总之,我们的研究探索了 TPPPA 可以诱导 ROS 过量产生,从而导致细胞凋亡,其介导的光动力疗法是SH-SY5Y细胞的高效治疗选择。与TMeQ自组装后[6],TPPPA保留了其凋亡途径诱导特性并充当载体,但这不利于TPPPA的光动力增强。

更新日期:2023-06-30
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