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负载抗单纯疱疹病毒2型人单克隆抗体的功能化聚乳酸-羟基乙酸共聚物纳米颗粒:早期诊断和靶向治疗的概念验证

Functionalized PLGA-Based Nanoparticles with Anti-HSV-2 Human Monoclonal Antibody: A Proof of Concept for Early Diagnosis and Targeted Therapy.

作者信息

Mariotti Melinda, Giacon Noah, Lo Cascio Ettore, Cacaci Margherita, Picchietti Simona, Di Vito Maura, Sanguinetti Maurizio, Arcovito Alessandro, Bugli Francesca

机构信息

Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

出版信息

Pharmaceutics. 2024 Sep 18;16(9):1218. doi: 10.3390/pharmaceutics16091218.

Abstract

Functionalized nanoparticles (NPs) represent a cutting edge in innovative clinical approaches, allowing for the delivery of selected compounds with higher specificity in a wider time frame. They also hold promise for novel theranostic applications that integrate both diagnostic and therapeutic functions. Pathogens are continuously evolving to try to escape the strategies designed to treat them. In this work, we describe the development of a biotechnological device, Nano-Immuno-Probes (NIPs), for early detection and infections treatment. Human Herpes Simplex Virus 2 was chosen as model pathogen. NIPs consist of PLGA-PEG-Sulfone polymeric NPs conjugated to recombinant Fab antibody fragments targeting the viral glycoprotein G2. NIPs synthesis involved multiple steps and was validated through several techniques. DLS analysis indicated an expected size increase with a good polydispersity index. Z-average and z-potential values were measured for PLGA-PEG-Bis-Sulfone NPs (86.6 ± 10.9 nm; -0.7 ± 0.3 mV) and NIPs (151 ± 10.4 nm; -5.1 ± 1.9 mV). SPR assays confirmed NIPs' specificity for the glycoprotein G2, with an apparent of 1.03 ± 0.61 µM. NIPs exhibited no cytotoxic effects on VERO cells at 24 and 48 h. This in vitro study showed that NIPs effectively target HSV-2, suggesting the potential use of these nanodevices to deliver both contrast agents as well as therapeutic compounds.

摘要

功能化纳米颗粒(NPs)代表了创新临床方法的前沿领域,能够在更广泛的时间范围内以更高的特异性递送选定的化合物。它们还为整合诊断和治疗功能的新型治疗诊断应用带来了希望。病原体在不断进化,试图逃避旨在治疗它们的策略。在这项工作中,我们描述了一种用于早期检测和感染治疗的生物技术设备——纳米免疫探针(NIPs)的开发。选择人类单纯疱疹病毒2作为模型病原体。NIPs由与靶向病毒糖蛋白G2的重组Fab抗体片段偶联的PLGA-PEG-砜聚合物纳米颗粒组成。NIPs的合成涉及多个步骤,并通过多种技术进行了验证。动态光散射(DLS)分析表明粒径有预期的增加,且具有良好的多分散指数。测量了PLGA-PEG-双砜纳米颗粒(86.6±10.9纳米;-0.7±0.3毫伏)和NIPs(151±10.4纳米;-5.1±1.9毫伏)的Z-平均粒径和Z-电位值。表面等离子体共振(SPR)分析证实了NIPs对糖蛋白G2的特异性,表观解离常数为1.03±0.61微摩尔。NIPs在24小时和48小时对VERO细胞无细胞毒性作用。这项体外研究表明,NIPs能有效靶向单纯疱疹病毒2,表明这些纳米装置有可能用于递送造影剂和治疗化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d74/11434782/a8f9d6a23fc2/pharmaceutics-16-01218-g001.jpg

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