Van Hees Sofie, Elbrink Kimberley, De Schryver Marjorie, Delputte Peter, Kiekens Filip
Department of Pharmaceutical Sciences, Laboratory for Pharmaceutical Technology and Biopharmacy, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Department of Biomedical Sciences, Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
J Nanopart Res. 2022;24(3):65. doi: 10.1007/s11051-022-05451-1. Epub 2022 Mar 14.
This research aims to evaluate different-sized nanoparticles consisting of (polyethylene glycol) (PEG) poly(lactic-co-glycolic acid) (PLGA), loaded with fluorescein isothiocyanate for nanoparticle uptake and intracellular fate in sialoadhesin-expressing macrophages, while being functionalized with anti-sialoadhesin antibody. Sialoadhesin is a macrophage-restricted receptor, expressed on certain populations of resident tissue macrophages, yet is also upregulated in some inflammatory conditions. The nanocarriers were characterized for nanoparticle size (84-319 nm), zeta potential, encapsulation efficiency, and in vitro dye release. Small (86 nm) antibody-functionalized PEG PLGA nanoparticles showed persisting benefit from sialoadhesin-targeting after 24 h compared to the control groups. For small (105 nm) PLGA nanoparticles, uptake rate was higher for antibody-conjugated nanoparticles, though the total amount of uptake was not enhanced after 24 h. For both plain and functionalized small-sized (PEG) PLGA nanoparticles, no co-localization between nanoparticles and (early/late) endosomes nor lysosomes could be observed after 1-, 4-, or 24-h incubation time. In conclusion, decorating (PEG) PLGA nanocarriers with anti-sialoadhesin antibodies positively impacts macrophage targeting, though it was found to be formulation-specific.
本研究旨在评估由聚乙二醇(PEG)-聚乳酸-羟基乙酸共聚物(PLGA)组成、负载异硫氰酸荧光素的不同尺寸纳米颗粒,以研究其在表达唾液酸粘附素的巨噬细胞中的纳米颗粒摄取及细胞内命运,同时用抗唾液酸粘附素抗体进行功能化修饰。唾液酸粘附素是一种巨噬细胞限制性受体,在某些驻留组织巨噬细胞群体上表达,但在某些炎症条件下也会上调。对纳米载体的纳米颗粒大小(84 - 319 nm)、zeta电位、包封效率和体外染料释放进行了表征。与对照组相比,小尺寸(86 nm)的抗体功能化PEG PLGA纳米颗粒在24小时后仍显示出唾液酸粘附素靶向的持续益处。对于小尺寸(105 nm)的PLGA纳米颗粒,抗体偶联纳米颗粒的摄取率更高,尽管24小时后摄取总量并未增加。对于普通和功能化的小尺寸(PEG)PLGA纳米颗粒,在孵育1、4或24小时后,均未观察到纳米颗粒与(早期/晚期)内体或溶酶体之间的共定位。总之,用抗唾液酸粘附素抗体修饰(PEG)PLGA纳米载体对巨噬细胞靶向有积极影响,尽管发现这具有制剂特异性。