Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 19 avenue Maistriau B-7000 Mons, Belgium.
Laboratoire Léon Brillouin, CNRS, CEA, Univ. Paris-Saclay, UMR12, F-91191 Gif sur Yvette, France.
J Mater Chem B. 2019 Jul 31;7(30):4692-4705. doi: 10.1039/c9tb00909d.
The present study reports the preparation of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) polymer vesicles via a nanoprecipitation method and the loading of two different size hydrophobically coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (a magnetic core size of 4.2 nm and 7.6 nm) into the membrane of these nanovesicles, whose thickness was measured precisely by small angle neutron scattering (SANS). Spherical nano-assemblies with a high USPIO payload and a diameter close to 150 nm were obtained as confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and cryo-TEM. The vesicular structure of these hybrid nano-assemblies was confirmed by multi-angle light scattering (MALS) measurements. Their magnetic properties were evaluated by T1 and T2 measurements (20 and 60 MHz) and by nuclear magnetic relaxation dispersion (NMRD) profiles. The size of USPIO entrapped in the membranes of PEO-b-PCL vesicles has a strong impact on their magnetic properties. It affects both their longitudinal and their transverse relaxivities and thus their magnetic resonance imaging (MRI) sensitivity. Acid-catalyzed hydrolysis of the PCL membrane also influences their relaxivities as shown by measurements carried out at pH 7 vs. pH 5. This property was used to monitor the membrane hydrolytic degradation in vitro, as a proof of concept of potential monitoring of drug delivery by nanomedicines in vivo and non-invasively, by MRI.
本研究报告了通过纳米沉淀法制备聚（氧化乙烯）-嵌段-聚（ε-己内酯）（PEO-b-PCL）聚合物囊泡，并将两种不同尺寸的疏水性包覆超小超顺磁性氧化铁（USPIO）纳米粒子（磁性核尺寸为 4.2nm 和 7.6nm）载入这些纳米囊泡的膜中，其厚度通过小角中子散射（SANS）精确测量。通过动态光散射（DLS）、透射电子显微镜（TEM）和冷冻 TEM 证实，得到了具有高 USPIO 载药量和接近 150nm 直径的球形纳米组装体。通过多角度光散射（MALS）测量证实了这些杂化纳米组装体的囊泡结构。通过 T1 和 T2 测量（20 和 60MHz）和核磁共振弛豫分散（NMRD）谱评估了它们的磁性能。嵌入 PEO-b-PCL 囊泡膜中的 USPIO 的尺寸对其磁性能有很强的影响。它影响它们的纵向和横向弛豫率，从而影响磁共振成像（MRI）的灵敏度。如在 pH 7 与 pH 5 下进行的测量所示，PCL 膜的酸催化水解也会影响其弛豫率。该性质用于体外监测膜的水解降解，作为体内和非侵入性监测纳米药物药物递送的潜在监测的概念验证，通过 MRI。
