The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation,ACS Applied Materials & Interfaces

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The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-06-21 , DOI: 10.1021/acsami.2c05054
Sarita Roy Bhattacharya ₁ , Kaushik Bhattacharya ₂ , Vanessa Joanne Xavier ₂ , Abolfazl Ziarati ₁ , Didier Picard ₂ , Thomas Bürgi ₁

Affiliation

Atomically precise gold nanoclusters (AuNCs) are an emerging class of quantum-sized nanomaterials with well-defined molecular structures and unique biophysical properties, rendering them highly attractive for biological applications. We set out to study the impact of different ligand shells of atomically similar nanoclusters on cellular recognition and response. To understand the effects of atomically precise nanoclusters with identical composition on cells, we selected two different water-soluble gold nanoclusters protected with captopril (Capt) and glutathione (GSH): Au₂₅(Capt)₁₈ (CNC) and Au₂₅(GSH)₁₈ (GNC), respectively. We demonstrated that a change of the ligand of the cluster completely changes its biological functions. Whereas both nanoclusters are capable of internalization, only CNC exhibits remarkable cytotoxicity, more specifically on cancer cells. CNC shows enhanced cytotoxicity by inhibiting the OXPHOS of mitochondria, possibly by inhibiting the ATP synthase complex of the electron transport chain (ETC), and by initiating the leakage of electrons into the mitochondrial lumen. The resulting increase in both mitochondrial and total cellular ROS triggers cell death indicated by the appearance of cellular markers of apoptosis. Remarkably, this effect of nanoclusters is independent of any external light source excitation. Our findings point to the prevailing importance of the ligand shell for applications of atomically precise nanoclusters in biology and medicine.

中文翻译：

原子精确的金/卡托普利纳米簇 Au25(Capt)18 通过抑制线粒体氧化磷酸化获得抗癌活性

原子精确的金纳米团簇（AuNC）是一类新兴的量子尺寸纳米材料，具有明确的分子结构和独特的生物物理性质，使其对生物应用极具吸引力。我们着手研究原子相似的纳米团簇的不同配体壳对细胞识别和响应的影响。为了了解具有相同成分的原子级精确纳米团簇对细胞的影响，我们选择了两种受卡托普利 (Capt) 和谷胱甘肽 (GSH) 保护的不同水溶性金纳米团簇：Au 25 (Capt) 18 (CNC)_和Au ₂₅ ( _GSH ) ₁₈（GNC），分别。我们证明，簇配体的变化完全改变了其生物学功能。虽然两种纳米簇都能够内化，但只有 CNC 表现出显着的细胞毒性，更具体地说是对癌细胞。CNC 通过抑制线粒体的 OXPHOS（可能是通过抑制电子传递链 (ETC) 的 ATP 合成酶复合物）以及启动电子泄漏到线粒体腔中来显示增强的细胞毒性。由此产生的线粒体和总细胞 ROS 的增加会引发细胞死亡，细胞凋亡标记物的出现表明了细胞死亡。值得注意的是，纳米团簇的这种效应与任何外部光源激发无关。

更新日期：2022-06-21

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