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小尺寸氧化石墨烯纳米片对人白细胞的生物学效应

Biological Effects of Small Sized Graphene Oxide Nanosheets on Human Leukocytes.

作者信息

Aventaggiato Michele, Valentini Federica, Caissutti Daniela, Relucenti Michela, Tafani Marco, Misasi Roberta, Zicari Alessandra, Di Martino Sara, Virtuoso Sara, Neri Anna, Mardente Stefania

机构信息

Department of Experimental Medicine, Sapienza University, Viale Regina Elena, 00161 Rome, Italy.

Department of Sciences and Chemical Technologies, Tor Vergata University, Via della Ricerca Scientifica 1, 00133 Rome, Italy.

出版信息

Biomedicines. 2024 Jan 23;12(2):256. doi: 10.3390/biomedicines12020256.

Abstract

Since the discovery of graphene, there has been a wide range of the literature dealing with its versatile structure and easy binding of biomolecules as well as its large loading capacity. In the emerging field of immunotherapy, graphene and its derivatives have potential uses as drug delivery platforms directly into tumour sites or as adjuvants in cancer vaccines, as they are internalized by monocytes which in turn may activate adaptive anti-tumoral immune responses. In this study, we expose cells of the innate immune system and a human acute monocytic leukemia cell line (THP-1) to low doses of small-sized GO nanosheets functionalized with bovine serum albumin (BSA) and fluorescein isothiocyanate (FITC), to study their acute response after internalization. We show by flow cytometry, uptake in cells of GO-BSA-FITC reaches 80% and cell viability and ROS production are both unaffected by exposure to nanoparticles. On the contrary, GO-BSA nanosheets seem to have an inhibitory effect on ROS production, probably due to their antioxidant properties. We also provided results on chemotaxis of macrophages derived from peripheral blood monocytes treated with GO-BSA. In conclusion, we showed the size of nanosheets, the concentration used and the degree of functionalization were important factors for biocompatibility of GO in immune cells. Its low cytotoxicity and high adaptability to the cells of the innate immune system make it a good candidate for deployment in immunotherapy, in particular for delivering protein antigens to monocytes which activate adaptive immunity.

摘要

自从石墨烯被发现以来,已有大量文献探讨其多样的结构、与生物分子的易结合性以及大负载能力。在新兴的免疫治疗领域,石墨烯及其衍生物有潜在用途,可作为直接输送到肿瘤部位的药物递送平台,或作为癌症疫苗中的佐剂,因为它们可被单核细胞内化,进而可能激活适应性抗肿瘤免疫反应。在本研究中,我们将先天免疫系统细胞和人急性单核细胞白血病细胞系(THP-1)暴露于低剂量的用牛血清白蛋白(BSA)和异硫氰酸荧光素(FITC)功能化的小尺寸氧化石墨烯纳米片,以研究其内化后的急性反应。我们通过流式细胞术表明,GO-BSA-FITC在细胞中的摄取率达到80%,且细胞活力和活性氧生成均不受纳米颗粒暴露的影响。相反,GO-BSA纳米片似乎对活性氧生成有抑制作用,可能是由于其抗氧化特性。我们还提供了用GO-BSA处理的外周血单核细胞来源的巨噬细胞趋化性的结果。总之,我们表明纳米片的尺寸、使用的浓度和功能化程度是氧化石墨烯在免疫细胞中生物相容性的重要因素。其低细胞毒性和对先天免疫系统细胞的高适应性使其成为免疫治疗中应用的良好候选物,特别是用于向激活适应性免疫的单核细胞递送蛋白质抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f500/10887315/59ec3ec18c59/biomedicines-12-00256-sch001.jpg

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