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通过增强自噬作用,用 Bi2WO6 纳米颗粒修饰针对白细胞介素-1β和 NLRP3 炎性体的 MWCNTs。

Modification of MWCNTs with Bi2WO6 nanoparticles targeting IL-1β and NLRP3 inflammasome via augmented autophagy.

机构信息

Ibn Sina University of Medical and Pharmaceutical Science, Baghdad, Iraq.

Department of Applied Sciences, University of Technology- Iraq, Baghdad, Iraq.

出版信息

PLoS One. 2024 Oct 31;19(10):e0309389. doi: 10.1371/journal.pone.0309389. eCollection 2024.

Abstract

This study reports the facile hydrothermal synthesis of pure Bi2WO6 and Bi2WO6\MWCNTs nanocomposite at specific molar ratio 1:2.5 of Bi2WO6:MWCNTs and elucidates their role in modulating the NLRP3 inflammasome pathway via autophagy induction. Comprehensive characterization techniques, including XRD, Raman, UV.Vis PL,FESEM,EDS and TEM, revealed the successful incorporation of MWCNTs into the Bi2WO6 structures, leading to enhanced crystattlinity, reduced band gap energy (2.4 eV) suppressed charge carrier recombination and mitigated nanoparticles aggregation. Notably, the reduced band gap facikitaed improved visible light harvesting, a crucial attribute for photocatalytic applications. Significantly, the nanocompsoite exhibited a remarkable capacity to augment autophagy in bone marrow-derived macrophages (BMDMs), consequently down-regulating the NLRP3 inflammasom activation and IL-1β secretion upon LPS and ATP stimulation. Immunofluorescence assays unveiled increased co-localization of LC3 and NLRP3, suggestion enhanced targeting of NLRP3 by autophagy. Inhibition of autophagy by 3-MA reversed these effects, confirming the pivotal role of autophagy induction. Furthermore, the nanocomposite attenuated caspase-1 activation and ASC oligomerzation, thereby impeding inflammasome assembly. Collectively, these findings underscore the potential of Bi2WO6\MWCNTs nanocompsite as a multifaceted therapeutic platform, levering its tailored optoelectronic properties and sbility to modulate the NLRP3 infalmmasome via autophagy augmentation. This work covers the way for the development of advanced nanomaterials with tunable functionalities for combating inflammatory disorders and antimicrobial applications.

摘要

本研究报告了一种简便的水热合成方法,可在特定摩尔比 1:2.5 的 Bi2WO6:MWCNTs 下合成纯 Bi2WO6 和 Bi2WO6\MWCNTs 纳米复合材料,并阐明了它们通过诱导自噬来调节 NLRP3 炎性体途径的作用。综合表征技术,包括 XRD、拉曼、紫外-可见 PL、FESEM、EDS 和 TEM,表明 MWCNTs 成功掺入 Bi2WO6 结构中,导致结晶度提高、带隙能降低(2.4 eV)、抑制载流子复合和减轻纳米颗粒聚集。值得注意的是,减小的带隙有利于提高可见光的捕获能力,这是光催化应用的关键属性。显著的是,该纳米复合物表现出增强骨髓来源巨噬细胞(BMDMs)自噬的能力,因此在 LPS 和 ATP 刺激下,NLRP3 炎性体的激活和 IL-1β 的分泌受到抑制。免疫荧光分析揭示了 LC3 和 NLRP3 的共定位增加,提示自噬对 NLRP3 的靶向增强。3-MA 抑制自噬逆转了这些效应,证实了自噬诱导的关键作用。此外,该纳米复合物抑制了 caspase-1 的激活和 ASC 的寡聚化,从而阻止了炎性体的组装。总之,这些发现强调了 Bi2WO6\MWCNTs 纳米复合物作为一种多功能治疗平台的潜力,利用其定制的光电特性和通过自噬增强来调节 NLRP3 炎性体的能力。这项工作为开发具有可调功能的先进纳米材料铺平了道路,可用于对抗炎症性疾病和抗菌应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e65/11527156/8ddd36e0367f/pone.0309389.g001.jpg

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