当前位置: X-MOL 学术Chem. Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Unveiling the interplay between homogeneous and heterogeneous catalytic mechanisms in copper–iron nanoparticles working under chemically relevant tumour conditions
Chemical Science ( IF 8.4 ) Pub Date : 2022-06-08 , DOI: 10.1039/d2sc01379g
Javier Bonet-Aleta 1, 2, 3 , Miguel Encinas-Gimenez 1, 2, 3 , Esteban Urriolabeitia 4 , Pilar Martin-Duque 2, 5, 6, 7 , Jose L Hueso 1, 2, 3, 6 , Jesus Santamaria 1, 2, 3, 6
Affiliation  

The present work sheds light on a generally overlooked issue in the emerging field of bio-orthogonal catalysis within tumour microenvironments (TMEs): the interplay between homogeneous and heterogeneous catalytic processes. In most cases, previous works dealing with nanoparticle-based catalysis in the TME focus on the effects obtained (e.g. tumour cell death) and attribute the results to heterogeneous processes alone. The specific mechanisms are rarely substantiated and, furthermore, the possibility of a significant contribution of homogeneous processes by leached species – and the complexes that they may form with biomolecules – is neither contemplated nor pursued. Herein, we have designed a bimetallic catalyst nanoparticle containing Cu and Fe species and we have been able to describe the whole picture in a more complex scenario where both homogeneous and heterogeneous processes are coupled and fostered under TME relevant chemical conditions. We investigate the preferential leaching of Cu ions in the presence of a TME overexpressed biomolecule such as glutathione (GSH). We demonstrate that these homogeneous processes initiated by the released by Cu–GSH interactions are in fact responsible for the greater part of the cell death effects found (GSH, a scavenger of reactive oxygen species, is depleted and highly active superoxide anions are generated in the same catalytic cycle). The remaining solid CuFe nanoparticle becomes an active catalyst to supply oxygen from oxygen reduced species, such as superoxide anions (by-product from GSH oxidation) and hydrogen peroxide, another species that is enriched in the TME. This activity is essential to sustain the homogeneous catalytic cycle in the oxygen-deprived tumour microenvironment. The combined heterogeneous–homogeneous mechanisms revealed themselves as highly efficient in selectively killing cancer cells, due to their higher GSH levels compared to healthy cell lines.

中文翻译:

揭示在化学相关肿瘤条件下工作的铜-铁纳米颗粒中均相和异相催化机制之间的相互作用

目前的工作揭示了肿瘤微环境 (TME) 中生物正交催化这一新兴领域中一个普遍被忽视的问题:均相和多相催化过程之间的相互作用。在大多数情况下,以前在 TME 中处理基于纳米粒子的催化的工作集中在获得的效果上(例如肿瘤细胞死亡)并将结果单独归因于异质过程。具体机制很少得到证实,此外,浸出物种以及它们可能与生物分子形成的复合物对均质过程的重大贡献的可能性既没有考虑也没有研究。在此,我们设计了一种含有 Cu 和 Fe 物种的双金属催化剂纳米颗粒,并且我们能够在更复杂的场景中描述整个画面,其中均相和非均相过程在 TME 相关的化学条件下耦合和促进。我们研究了在 TME 过表达的生物分子(如谷胱甘肽 (GSH))存在下铜离子的优先浸出。我们证明,这些由 Cu-GSH 相互作用释放的均质过程实际上是造成大部分细胞死亡效应的原因(GSH,一种活性氧的清除剂,被耗尽并在细胞中产生高活性超氧阴离子)相同的催化循环)。剩余的固体 CuFe 纳米颗粒成为活性催化剂,从氧还原物质中提供氧气,例如超氧阴离子(GSH 氧化的副产物)和过氧化氢,另一种富含 TME 的物质。这种活性对于维持缺氧肿瘤微环境中的均匀催化循环至关重要。由于与健康细胞系相比,它们的 GSH 水平更高,因此结合的异质 - 均质机制表明它们在选择性杀死癌细胞方面非常有效。
更新日期:2022-06-08
down
wechat
bug