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铜/锡纳米复合材料负载的外泌体诱导皮肤癌细胞系发生细胞凋亡和 G0/G1 期细胞周期阻滞。

Copper/Tin Nanocomposites-Loaded Exosomes Induce Apoptosis and Cell Cycle Arrest at G0/G1 Phase in Skin Cancer Cell Line.

机构信息

Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, Egypt.

Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, 12622, Egypt.

出版信息

Chem Biodivers. 2024 Aug;21(8):e202400486. doi: 10.1002/cbdv.202400486. Epub 2024 Jul 30.

Abstract

This study aims to explore the efficacy of Copper/Tin (CuS/SnS) nanocomposites loaded into exosomes against skin cancer A431 cell line. CuS/SnS nanocomposites (S1, S2, S3) were synthesized and characterized, then loaded into exosomes (Exo) (S1-Exo, S2-Exo and S3-Exo) and characterized. After that, the loaded samples were investigated in vitro against A431 using cytotoxicity, apoptosis, and cell cycle assays. CuS/SnS nanocomposites were indexed to hexagonal CuS structure and orthorhombic α-SnS phase and showed nano-rode shape. The exosomes loaded with nanocomposites were regular and rounded within the size of 120 nm, with no signs of broken exosomes or leakage of their contents. The cytotoxicity assay indicated the enhanced cytotoxic of S1-Exo versus the free nano-form S1 on A431. Interestingly, S1-Exo recorded 1.109 times more than DOX in its anti-skin cancer capacity. Moreover, S1-Exo recorded 40.2 % for early apoptosis and 22.1 % for late apoptosis. Furthermore, it displayed impact in arresting the cancer cell cycle at G0/G1 phase and reducing G2/M phase. Noteworthy, loaded nanocomposites were safe against normal HSF skin cells. In conclusion, the loaded CuS/SnS nanocomposites into the exosomes could be of great potential as anti-skin cancer candidates through induction of apoptosis and promotion of the cell cycle arrest at G0/G1 phase.

摘要

本研究旨在探索负载铜/锡(CuS/SnS)纳米复合材料的外泌体对皮肤癌细胞系 A431 的疗效。合成并表征了 CuS/SnS 纳米复合材料(S1、S2、S3),然后将其负载到外泌体(Exo)中(S1-Exo、S2-Exo 和 S3-Exo)并进行了表征。之后,通过细胞毒性、细胞凋亡和细胞周期检测,在体外对负载样品进行了 A431 细胞的研究。CuS/SnS 纳米复合材料被指认为具有六方 CuS 结构和正交 α-SnS 相的纳米棒形状。负载纳米复合材料的外泌体呈规则的圆形,大小在 120nm 左右,没有外泌体破裂或内容物泄漏的迹象。细胞毒性试验表明,与游离纳米形式的 S1 相比,S1-Exo 对 A431 的细胞毒性增强。有趣的是,S1-Exo 的抗癌能力比 DOX 高 1.109 倍。此外,S1-Exo 记录到 40.2%的早期凋亡和 22.1%的晚期凋亡。此外,它还显示出在将癌细胞周期阻滞在 G0/G1 期并减少 G2/M 期方面的作用。值得注意的是,负载的纳米复合材料对正常 HSF 皮肤细胞是安全的。总之,负载到外泌体中的 CuS/SnS 纳米复合材料通过诱导细胞凋亡和促进细胞周期阻滞在 G0/G1 期,可能具有作为抗癌候选物的巨大潜力。

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