Translational Nanobiomaterials and Imaging Group, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, the Netherlands.
Mikrochim Acta. 2022 Sep 3;189(10):368. doi: 10.1007/s00604-022-05441-z.
Upconversion nanoparticles (UCNPs) represent a group of NPs that can convert near-infrared (NIR) light into ultraviolet and visible light, thus possess deep tissue penetration power with less background fluorescence noise interference, and do not induce damage to biological tissues. Due to their unique optical properties and possibility for surface modification, UCNPs can be exploited for concomitant antigen delivery into dendritic cells (DCs) and monitoring by molecular imaging. In this study, we focus on the development of a nano-delivery platform targeting DCs for immunotherapy and simultaneous imaging. OVA 254-267 (OVA24) peptide antigen, harboring a CD8 T cell epitope, and Pam3CysSerLys4 (Pam3CSK4) adjuvant were chemically linked to the surface of UCNPs by amide condensation to stimulate DC maturation and antigen presentation. The OVA24-Pam3CSK4-UCNPs were thoroughly characterized and showed a homogeneous morphology and surface electronegativity, which promoted a good dispersion of the NPs. In vitro experiments demonstrated that OVA24-Pam3CSK4-UCNPs induced a strong immune response, including DC maturation, T cell activation, and proliferation, as well as interferon gamma (IFN-γ) production. In vivo, highly sensitive upconversion luminescence (UCL) imaging of OVA24-Pam3CSK4-UCNPs allowed tracking of UCNPs from the periphery to lymph nodes. In summary, OVA24-Pam3CSK4-UCNPs represent an effective tool for DC-based immunotherapy.
上转换纳米粒子(UCNPs)代表了一类能够将近红外(NIR)光转化为紫外和可见光的纳米粒子,因此具有深层组织穿透能力,背景荧光噪声干扰较小,且不会对生物组织造成损伤。由于其独特的光学性质和表面修饰的可能性,UCNPs 可用于同时将抗原递送至树突状细胞(DCs)并进行分子成像监测。在这项研究中,我们专注于开发一种针对 DCs 的纳米递药平台,用于免疫治疗和同时成像。OVA 254-267(OVA24)肽抗原,含有 CD8 T 细胞表位,以及 Pam3CysSerLys4(Pam3CSK4)佐剂,通过酰胺缩合化学连接到 UCNPs 的表面,以刺激 DC 成熟和抗原呈递。OVA24-Pam3CSK4-UCNPs 经过了全面的表征,显示出均匀的形态和表面电负性,这促进了 NPs 的良好分散。体外实验表明,OVA24-Pam3CSK4-UCNPs 诱导了强烈的免疫反应,包括 DC 成熟、T 细胞激活和增殖,以及干扰素γ(IFN-γ)的产生。在体内,对 OVA24-Pam3CSK4-UCNPs 的高灵敏度上转换发光(UCL)成像允许从外周追踪 UCNPs 到淋巴结。总之,OVA24-Pam3CSK4-UCNPs 代表了一种用于基于 DC 的免疫治疗的有效工具。