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纳米材料对血浆成分(免疫球蛋白和凝血因子VIII)影响的研究综述:2010 - 2020年回顾

An overview on the investigation of nanomaterials' effect on plasma components: immunoglobulins and coagulation factor VIII, 2010-2020 review.

作者信息

Zadeh Mehrizi Tahereh, Mousavi Hosseini Kamran

机构信息

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine Tehran Iran

出版信息

Nanoscale Adv. 2021 May 18;3(13):3730-3745. doi: 10.1039/d1na00119a. eCollection 2021 Jun 30.

Abstract

FVIII and immunoglobulins (Igs) are the most prominent plasma proteins, which play a vital role in plasma hemostasis. These proteins have been implemented frequently in protein therapy. Therefore, their maintenance, durability, and stability are highly essential. Herein, various approaches to improve protein functions have been investigated, such as using recombinant protein replacement. In comparison, advances in nanotechnology have provided adequate context to boost biomaterial utilization. In this regard, the applications of various nanoparticles such as polymeric nanomaterials (PEG and PLGA), metal nanoparticles, dendrimers, and lipid based nanomaterials (liposomes and lipid nanoparticles) in stability and the functional improvement of antibodies and coagulation factor VIII (FVIII) have been reviewed from 2010 to 2020. Reviewing related articles has shown that not only can nanomaterials adequately protect the structure of proteins, but have also improved proteins' functions in some cases. For example, the high rate of FVIII instability has been successfully enhanced by bio-PEGylation. Also, utilizing PEGylated liposomes, using the PEG-lip technique for coating nanostructures, leads to FIIIV half-life prolongation. Hence, PEGylation had most impact on the stability of FVIII. Likewise, PEG-coated liposome nano-carriers also presented such a good effect on stability improvements for FVIII due to their ability to tune the immune system by reducing FVIII immunogenicity. Similarly, Ig PEGylation and conjugation to magnetic nanoparticles resulted in increased half-life and better purification of Igs, respectively, without any loss in structural or functional features. Consequently, metal-organic frameworks and recent hybrid systems have been introduced as promising nanomaterials in biomedical applications. As far as we know, this is the first study in this field, which considers the applications of nanoparticles for improving the storage and stability of antibodies and coagulation FVIII.

摘要

凝血因子VIII(FVIII)和免疫球蛋白(Igs)是最主要的血浆蛋白,在血浆止血过程中发挥着至关重要的作用。这些蛋白在蛋白质治疗中经常被应用。因此,它们的维持、耐久性和稳定性至关重要。在此,人们研究了各种改善蛋白质功能的方法,比如使用重组蛋白替代。相比之下,纳米技术的进步为提高生物材料的利用率提供了充分的条件。在这方面,综述了2010年至2020年各种纳米颗粒,如聚合物纳米材料(聚乙二醇和聚乳酸-羟基乙酸共聚物)、金属纳米颗粒、树枝状大分子和脂质基纳米材料(脂质体和脂质纳米颗粒)在抗体和凝血因子VIII(FVIII)稳定性及功能改善方面的应用。对相关文章的综述表明,纳米材料不仅能充分保护蛋白质的结构,而且在某些情况下还能改善蛋白质的功能。例如,通过生物聚乙二醇化成功提高了FVIII的高不稳定性。此外,利用聚乙二醇化脂质体,采用聚乙二醇-脂质技术包覆纳米结构,可延长FVIII的半衰期。因此,聚乙二醇化对FVIII的稳定性影响最大。同样,聚乙二醇包覆的脂质体纳米载体也因其能够通过降低FVIII免疫原性来调节免疫系统,从而对FVIII的稳定性改善呈现出良好效果。类似地,Ig的聚乙二醇化和与磁性纳米颗粒的偶联分别导致半衰期延长和Ig的更好纯化,且结构或功能特性均无任何损失。因此,金属有机框架和最近的混合系统已被引入作为生物医学应用中有前景的纳米材料。据我们所知,这是该领域的第一项研究,考虑了纳米颗粒在改善抗体和凝血因子FVIII的储存及稳定性方面的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d08/9419877/c41b5ce08321/d1na00119a-f1.jpg

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