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纳米颗粒和纳米胶体碳:它们会成为下一类针对 2 型糖尿病中人类胰岛淀粉样多肽纤维形成和聚集的抗糖尿病药物吗?

Nanoparticles and Nanocolloidal Carbon: Will They Be the Next Antidiabetic Class That Targets Fibrillation and Aggregation of Human Islet Amyloid Polypeptide in Type 2 Diabetes?

机构信息

Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520 - IEMN, F-59000 Lille, France.

出版信息

Acc Chem Res. 2022 Oct 18;55(20):2869-2881. doi: 10.1021/acs.accounts.2c00415. Epub 2022 Sep 29.

Abstract

Nanotechnology is revolutionizing human medicine. Nanoparticles (NPs) are currently used for treating various cancers, for developing vaccines, and for imaging, and other promises offered by NPs might come true soon. Due to the interplay between NPs and proteins, there is more and more evidence supporting the role of NPs for treating amyloid-based diseases. NPs can induce some conformational changes of the adsorbed protein molecules via various molecular interactions, leading to inhibition of aggregation and fibrillation of several and different amyloid proteins. Though an in depth understanding of such interactions between NPs and amyloid structures is still lacking, the inhibition of protein aggregation by NPs represents a new generation of innovative and effective medicines to combat metabolic diseases such as type 2 diabetes (T2D). Here, we lay out advances made in the field of T2D notably for optimizing protein aggregation inhibition strategies. This Account covers discussions about the current understanding of β-cells, the insulin producing cells within the pancreas, under diabetic conditions, notably increased glucose and fatty acid levels, and the implication of these conditions on the formation of human islet amyloid polypeptide (hIAPP) amylin oligomers and aggregates. Owing to the great potential of carbon nanostructures to interfere with protein aggregation, an important part of this Account will be devoted to the state of the art of therapeutic options in the form of emerging nanomaterials-based amyloidosis inhibitors. Our group has recently made some substantial progress in this regard by investigating the impact of glucose and fatty acid concentrations on hIAPP aggregation and β-cell toxicity. Furthermore, the great potential of carbon nanocolloids in reversing hIAPP aggregation under diabetic conditions will be highlighted as the approach has been validated on β-cell cultures from rats. We hope that this Account will evoke new ideas and concepts in this regard. We give some lead references below on pancreatic β-cell aspects and carbon quantum dots for managing diabetics and nanomedicine related aspects, a topic of interest in our laboratory.

摘要

纳米技术正在彻底改变人类医学。纳米粒子(NPs)目前被用于治疗各种癌症、开发疫苗和进行成像,而 NPs 所带来的其他承诺也即将成为现实。由于 NPs 与蛋白质之间的相互作用,越来越多的证据支持 NPs 用于治疗淀粉样蛋白相关疾病。NPs 可以通过各种分子相互作用诱导吸附蛋白分子发生一些构象变化,从而抑制几种不同的淀粉样蛋白的聚集和纤维化。尽管人们对 NPs 与淀粉样结构之间的这种相互作用的理解还不够深入,但 NPs 抑制蛋白质聚集代表了一种用于对抗代谢疾病(如 2 型糖尿病(T2D))的新型、有效的创新药物。在这里,我们概述了在 T2D 领域取得的进展,特别是在优化蛋白质聚集抑制策略方面。本账户涵盖了对胰腺中产生胰岛素的β细胞在糖尿病条件下的当前理解,特别是葡萄糖和脂肪酸水平的增加,以及这些条件对人胰岛淀粉样多肽(hIAPP)淀粉样蛋白寡聚体和聚集体形成的影响。由于碳纳米结构在干扰蛋白质聚集方面具有巨大的潜力,因此本账户的一个重要部分将致力于新兴纳米材料基淀粉样变抑制剂治疗选择的最新进展。我们小组最近在这方面取得了一些实质性的进展,研究了葡萄糖和脂肪酸浓度对 hIAPP 聚集和β细胞毒性的影响。此外,在糖尿病条件下逆转 hIAPP 聚集的碳纳米胶体的巨大潜力将被突出,因为这种方法已经在大鼠β细胞培养物上得到了验证。我们希望本账户能在这方面引发新的想法和概念。我们在下面提供了一些关于胰腺β细胞方面和用于管理糖尿病和纳米医学相关方面的碳量子点的参考文献,这是我们实验室感兴趣的一个主题。

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