Leiden Institute of Chemistry, Leiden University, The Netherlands.
Leiden Institute of Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, The Netherlands.
Biomaterials. 2018 Jun;168:54-63. doi: 10.1016/j.biomaterials.2018.03.037. Epub 2018 Mar 22.
The long-term fate of biomedical nanoparticles after endocytosis is often only sparsely addressed in vitro and in vivo, while this is a crucial parameter to conclude on their utility. In this study, dual-fluorescent polyisobutylene-polyethylene glycol (PiB-PEG) polymersomes were studied for several days in vitro and in vivo. In order to optically track the vesicles' integrity, one fluorescent probe was located in the membrane and the other in the aqueous interior compartment. These non-toxic nanovesicles were quickly endocytosed in living A549 lung carcinoma cells but unusually slowly transported to perinuclear lysosomal compartments, where they remained intact and luminescent for at least 90 h without being exocytosed. Fluorescence-assisted flow cytometry indicated that after endocytosis, the nanovesicles were eventually degraded within 7-11 days. In zebrafish embryos, the polymersomes caused no lethality and were quickly taken up by the endothelial cells, where they remained fully intact for as long as 96 h post-injection. This work represents a novel case-study of the remarkable potential of PiB-PEG polymersomes as an in vivo bio-imaging and slow drug delivery platform.
生物医学纳米颗粒被细胞内吞后的长期命运在体外和体内通常都研究得很少，而这是推断其效用的关键参数。在这项研究中，双荧光聚异丁烯-聚乙二醇（PiB-PEG）聚合物囊泡在体外和体内进行了几天的研究。为了光学追踪囊泡的完整性，一个荧光探针位于膜中，另一个位于水相内部隔室。这些无毒的纳米囊泡在活的 A549 肺癌细胞中被迅速内吞，但异常缓慢地转运到核周溶酶体隔室，在那里它们保持完整和发光至少 90 小时而不被外排。荧光辅助流式细胞术表明，内吞作用后，纳米囊泡在 7-11 天内最终被降解。在斑马鱼胚胎中，聚合物囊泡没有引起致死性，并被内皮细胞迅速摄取，在注射后长达 96 小时内它们保持完全完整。这项工作代表了 PiB-PEG 聚合物囊泡作为体内生物成像和缓慢药物传递平台的显著潜力的一个新的案例研究。
