Efficient gene delivery to immune cells via a recombinant multifunctional chimeric peptide nanocarrier: Implications in immunotherapy

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2025-06-16 DOI:10.1016/j.nano.2025.102837

Mahdiyar Dehshiri MSc , Fateme Zarein MSc , Fatemeh Rajabi MSc , Mohammad Reza Javan PhD , Maryam Nikkhah PhD , Fatemeh Rahbarizadeh PhD , Jalil Mehrzad PhD, DVM , Seyed Mohammad Moazzeni PhD , Amir Ali Hamidieh MD , Saman Hosseinkhani PhD

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Abstract

Genetic modification of immune cells remains a major challenge in immunotherapy. While viral and non-viral carriers exist, low gene transfer efficiency persists with non-viral methods. We present a peptide-based carrier (MiRGD) for gene delivery to diverse immune cells. The MiRGD/plasmid complex formation was characterized via gel retardation, dynamic light scattering, and zeta potential analysis. After safety and efficiency optimization in HEK293T cells, MiRGD achieved 69 % chimeric antigen receptor (CAR) transfection in Jurkat T cells (>98 % viability) and 28 % in primary human T cells. Dendritic cells showed 61 % transfection with >85 % viability. In vivo, MiRGD functioned as a DNA vaccine against SARS-CoV-2, eliciting robust antibody titers, neutralization, and safe histopathology. These results demonstrate MiRGD's efficacy and biocompatibility for immune cell engineering (T cells, dendritic cells, macrophages) and vaccination, offering a cost-effective, non-toxic platform for immunotherapy applications.

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通过重组多功能嵌合肽纳米载体有效地向免疫细胞传递基因：在免疫治疗中的意义

免疫细胞的遗传修饰仍然是免疫治疗的主要挑战。虽然存在病毒和非病毒载体，但非病毒方法的基因转移效率仍然很低。我们提出了一种基于肽的载体（MiRGD），用于基因递送到不同的免疫细胞。通过凝胶阻滞、动态光散射和zeta电位分析表征了MiRGD/质粒复合物的形成。经过在HEK293T细胞中的安全性和效率优化，MiRGD在Jurkat T细胞中实现了69%的嵌合抗原受体（CAR）转染（98%的存活率），在原代人T细胞中实现了28%的转染。树突状细胞转染61%，存活率85%。在体内，MiRGD作为针对SARS-CoV-2的DNA疫苗发挥作用，引发强大的抗体滴度，中和和安全的组织病理学。这些结果证明了MiRGD在免疫细胞工程（T细胞、树突状细胞、巨噬细胞）和疫苗接种方面的有效性和生物相容性，为免疫治疗应用提供了一个成本效益高、无毒的平台。

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

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.