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基于聚丙烯酸和藻类细胞壁生物聚合物的硫醇化纳米颗粒的合成与表征,用于递送严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的受体结合域

Synthesis and Characterization of Thiolated Nanoparticles Based on Poly (Acrylic Acid) and Algal Cell Wall Biopolymers for the Delivery of the Receptor Binding Domain from SARS-CoV-2.

作者信息

García-Silva Ileana, Farfán-Castro Susan, Rosales-Mendoza Sergio, Palestino Gabriela

机构信息

Biotechnology Section, Center for Research in Health Science and Biomedicine, Autonomous University of San Luis Potosí, Av. Sierra Leona 550, Lomas de San Luis, San Luis Potosí 78210, Mexico.

Biopolymers and Nanostructures Laboratory, School of Chemical Sciences, Autonomous University of San Luis Potosí, Manuel Nava 6, Av. Dr. Manuel Nava, Zona Universitaria, San Luis Potosí 78210, Mexico.

出版信息

Pharmaceutics. 2024 Jul 2;16(7):891. doi: 10.3390/pharmaceutics16070891.

DOI:10.3390/pharmaceutics16070891
PMID:39065588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11279463/
Abstract

The COVID-19 pandemic required great efforts to develop efficient vaccines in a short period of time. However, innovative vaccines against SARS-CoV-2 virus are needed to achieve broad immune protection against variants of concern. Polymeric-based particles can lead to innovative vaccines, serving as stable, safe and immunostimulatory antigen delivery systems. In this work, polymeric-based particles called thiolated PAA/Schizo were developed. Poly (acrylic acid) (PAA) was thiolated with cysteine ethyl ester and crosslinked with a sp. cell wall fraction under an inverse emulsion approach. Particles showed a hydrodynamic diameter of 313 ± 38 nm and negative Zeta potential. FT-IR spectra indicated the presence of coconut oil in thiolated PAA/Schizo particles, which, along with the microalgae, could contribute to their biocompatibility and bioactive properties. TGA analysis suggested strong interactions between the thiolated PAA/Schizo components. In vitro assessment revealed that thiolated particles have a higher mucoadhesiveness when compared with non-thiolated particles. Cell-based assays revealed that thiolated particles are not cytotoxic and, importantly, increase TNF-α secretion in murine dendritic cells. Moreover, immunization assays revealed that thiolated PAA/Schizo particles induced a humoral response with a more balanced IgG2a/IgG1 ratio. Therefore, thiolated PAA/Schizo particles are deemed a promising delivery system whose evaluation in vaccine prototypes is guaranteed.

摘要

新冠疫情需要在短时间内付出巨大努力来研发高效疫苗。然而,需要针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒的创新疫苗,以实现针对关注变体的广泛免疫保护。基于聚合物的颗粒可促成创新疫苗,作为稳定、安全且具有免疫刺激作用的抗原递送系统。在这项工作中,研发了一种名为硫醇化聚丙烯酸/裂殖壶菌(thiolated PAA/Schizo)的基于聚合物的颗粒。聚丙烯酸(PAA)用半胱氨酸乙酯进行硫醇化,并在反相乳液法下与裂殖壶菌细胞壁组分交联。颗粒的流体动力学直径为313±38纳米,zeta电位为负。傅里叶变换红外光谱(FT-IR)表明硫醇化PAA/Schizo颗粒中存在椰子油,这与微藻一起,可能有助于其生物相容性和生物活性特性。热重分析(TGA)表明硫醇化PAA/Schizo各组分之间存在强相互作用。体外评估显示,与未硫醇化的颗粒相比,硫醇化颗粒具有更高的黏膜粘附性。基于细胞的检测表明硫醇化颗粒没有细胞毒性,重要的是,可增加小鼠树突状细胞中肿瘤坏死因子-α(TNF-α)的分泌。此外,免疫检测表明硫醇化PAA/Schizo颗粒诱导的体液反应具有更平衡的IgG2a/IgG1比值。因此,硫醇化PAA/Schizo颗粒被认为是一种有前景的递送系统,保证在疫苗原型中对其进行评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/5d777059c239/pharmaceutics-16-00891-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/475145741700/pharmaceutics-16-00891-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/ce1a18fece6f/pharmaceutics-16-00891-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/1cafc492604f/pharmaceutics-16-00891-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/efa9866647f1/pharmaceutics-16-00891-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/eabef911f3ea/pharmaceutics-16-00891-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/5d777059c239/pharmaceutics-16-00891-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/392e9cd2468a/pharmaceutics-16-00891-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/781493068dcd/pharmaceutics-16-00891-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/5f007960fcab/pharmaceutics-16-00891-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/ce1a18fece6f/pharmaceutics-16-00891-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/1cafc492604f/pharmaceutics-16-00891-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/efa9866647f1/pharmaceutics-16-00891-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/eabef911f3ea/pharmaceutics-16-00891-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/935d/11279463/5d777059c239/pharmaceutics-16-00891-g009.jpg

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