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NFL-TBS.40-63肽的自组装及其作为胶质母细胞瘤递送剂与金纳米颗粒相互作用的研究

Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.

作者信息

Alnemeh-Al Ali H, Griveau A, Artzner F, Dupont A, Lautram N, Jourdain M A, Eyer J

机构信息

Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.

Univ Rennes, CNRS, IPR (Institut de Physique de Rennes), UMR 6251, F-35000 Rennes, France.

出版信息

Int J Pharm X. 2022 Sep 22;4:100128. doi: 10.1016/j.ijpx.2022.100128. eCollection 2022 Dec.

Abstract

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

摘要

NFL-TBS.40-63肽是一种最近发现的源自轻神经丝链(NFL)的肽。在本研究中,我们证明了生物素化的NFL肽(BIOT-NFL)在几种溶液中能自发自组装成排列良好的纳米纤维(宽度约5纳米,长度为几微米),而从其他有或没有偶联的肽中未系统观察到典型的自组装现象。通过表面张力测量确定使BIOT-NFL肽聚集和自缔合的临界聚集浓度为10摩尔/升。BIOT-NFL肽的X射线散射也证明了其β-折叠结构,该结构可促进自组装过程中涉及的分子间相互作用。通过透析膜研究考察了自组装的BIOT-NFL肽纳米纤维可能的解体情况。我们进一步研究了BIOT-NFL肽形成的纳米纤维与金纳米颗粒之间的相互作用。有趣的是,这些纳米颗粒与BIOT-NFL肽之间表现出强烈的相互作用,导致形成了被金纳米颗粒大量装饰的BIOT-NFL肽纳米纤维。最后,我们研究了与BIOT-NFL纳米纤维偶联的金纳米颗粒内化进入F98大鼠胶质母细胞瘤细胞的情况,与未偶联的对照金纳米颗粒相比,其内化增加。所有这些结果表明,这种肽可能是一种有前景的靶向递送治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af9b/9529584/2827466e208e/ga1.jpg

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