Polyethylenimine-Conjugated Au-NPs as an Efficient Vehicle for in vitro and in vivo DNA Vaccine Delivery.

IF 6.6 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI:10.2147/IJN.S493211

Aras Kartouzian, Alexandra Heiz, Kamyar Shameli, Hassan Moeini

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引用次数: 0

Abstract

Purpose: This study aimed to develop green-synthesized gold nanoparticles (Au-NPs) conjugated with polyethyleneimine (PEI) to overcome challenges in intracellular DNA vaccine delivery, focusing on enhancing cellular uptake and immune responses against the human norovirus (HuNoV) GII.4 variants.

Methods: Au-NPs were synthesized using a citrate-ion-mediated green approach, with size and morphology analyzed via UV-vis spectroscopy and transmission electron microscopy (TEM). Stability was evaluated through zeta potential measurements. PEI conjugation was employed to modify surface charge. After in vitro evaluation of pDNA delivery efficiency and cytotoxicity in HEK293 cells, PEI-coated Au-NPs loaded with a HuNoV GII.4 pDNA vaccine (AuPEI-NPs-pDNA) were assessed for the immune responses in mice.

Results: UV-vis spectroscopy and TEM confirmed successful Au-NP synthesis. Zeta potential shifted from -31.38 mV to -20.60 mV, reflecting stable but slightly reduced colloidal stability with larger sizes. PEI conjugation reversed surface charge to positive, enabling 100% transfection efficacy in HEK293 cells by day two without cytotoxicity. The AuPEI-NPs-pDNA induced significantly higher NoV-specific IgG antibodies and T-cell responses compared to unmodified Au-NPs, highlighting the role of positive charge in enhancing cellular uptake and immune activation. These results underscore PEI-coated Au-NPs as a biocompatible, efficient platform for DNA vaccine delivery.

Conclusion: PEI-coated Au-NPs demonstrate exceptional potential as non-toxic, high-efficiency carriers for DNA vaccines, enabling robust humoral and cellular immune responses. This strategy holds promises for advancing gene therapy and combating rapidly evolving pathogens like HuNoV, with broader applications in targeted drug delivery.

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聚乙烯亚胺偶联Au-NPs作为体外和体内DNA疫苗递送的有效载体

目的：本研究旨在开发与聚乙烯亚胺（PEI）结合的绿色合成金纳米颗粒（Au-NPs），以克服细胞内DNA疫苗递送的挑战，重点是增强细胞摄取和针对人诺如病毒（HuNoV） GII.4变体的免疫反应。方法：采用柠檬酸盐离子介导的绿色方法合成Au-NPs，通过紫外可见光谱和透射电子显微镜（TEM）分析其大小和形态。通过zeta电位测量来评估稳定性。采用PEI共轭法修饰表面电荷。在体外评估了pDNA在HEK293细胞中的传递效率和细胞毒性后，我们评估了pei包被的携带HuNoV GII.4 pDNA疫苗（AuPEI-NPs-pDNA）的Au-NPs在小鼠中的免疫反应。结果：紫外可见光谱和透射电镜证实成功合成了Au-NP。Zeta电位从-31.38 mV变化到-20.60 mV，反映了较大尺寸的胶体稳定性稳定但略有降低。PEI偶联使表面电荷逆转为阳性，使HEK293细胞在第2天的转染效率达到100%，无细胞毒性。与未修饰的Au-NPs相比，AuPEI-NPs-pDNA诱导了更高的nov特异性IgG抗体和t细胞反应，突出了正电荷在增强细胞摄取和免疫激活方面的作用。这些结果强调pei包被的Au-NPs是一种生物相容性好的、高效的DNA疫苗递送平台。结论：pei包被的Au-NPs显示出作为DNA疫苗无毒、高效载体的特殊潜力，可实现强大的体液和细胞免疫反应。这一策略有望推进基因治疗和对抗HuNoV等快速进化的病原体，并在靶向药物输送方面有更广泛的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.