Département de génie des mines, de la métallurgie et des matériaux, Centre de recherche sur les matériaux avancés (CERMA), Université Laval, Québec G1V 0A6, Canada.
Axe Médecine régénératrice, Centre Hospitalier Universitaire (CHU) de Québec, 2705, boul. Laurier (T1-61a), Québec G1V 4G2, Canada.
Bioconjug Chem. 2021 Apr 21;32(4):729-745. doi: 10.1021/acs.bioconjchem.1c00017. Epub 2021 Mar 10.
Ultrasmall nanoparticles (US-NPs; <20 nm in hydrodynamic size) are now included in a variety of pharmacological and cosmetic products, and new technologies are needed to detect at high sensitivity the passage of small doses of these products across biological barriers such as the skin. In this work, a diffusion cell adapted to positron emission tomography (PET), a highly sensitive imaging technology, was developed to measure the passage of gold NPs (AuNPs) in skin samples in continuous mode. US-AuNPs (3.2 nm diam.; TEM) were functionalized with deferoxamine (DFO) and radiolabeled with Zr (half-life: 3.3 days, matching the timeline of diffusion tests). The physicochemical properties of the functionalized US-AuNPs (US-AuNPs-PEG-DFO) were characterized by FTIR (DFO grafting; hydroxamate peaks: 1629.0 cm, 1569.0 cm), XPS (presence of the O═C-N C 1s peak of DFO at 287.49 eV), and TGA (organic mass fraction). The passage of US-AuNPs-PEG-DFO-Zr in skin samples was measured by PET, and the diffusion parameters were extracted thereby. The signals of radioactive US-AuNPs-PEG-DFO-Zr leaving the donor compartment, passing through the skin, and entering the acceptor compartment were detected in continuous at concentrations as low as 2.2 nM of Au. The high-sensitivity acquisitions performed in continuous allowed for the first time to extract the lag time to the start of permeation, the lag time to start of the steady state, the diffusion coefficients, and the influx data for AuNPs permeating into the skin. PET could represent a highly valuable tool for the development of nanoparticle-containing topical formulations of drugs and cosmetics.
超小纳米粒子（US-NPs；水动力直径<20nm）现被应用于多种药理学和化妆品产品中，因此需要新技术来高灵敏度地检测这些产品以小剂量穿过生物屏障，如皮肤。在这项工作中，开发了一种适应正电子发射断层扫描（PET）的扩散池，这是一种高灵敏度的成像技术，用于以连续模式测量金纳米粒子（AuNPs）在皮肤样品中的渗透。US-AuNPs（3.2nm 直径；TEM）被去铁胺（DFO）功能化，并被 Zr 放射性标记（半衰期：3.3 天，与扩散试验的时间线匹配）。功能化的 US-AuNPs（US-AuNPs-PEG-DFO）的理化性质通过傅里叶变换红外光谱（DFO 接枝；羟肟酸峰：1629.0cm，1569.0cm）、X 射线光电子能谱（DFO 的 O ═ C-N C 1s 峰在 287.49eV 处存在）和热重分析（有机质量分数）进行了表征。通过 PET 测量了 US-AuNPs-PEG-DFO-Zr 在皮肤样品中的渗透，并提取了扩散参数。放射性 US-AuNPs-PEG-DFO-Zr 离开供体隔室、穿过皮肤并进入受体隔室的信号在浓度低至 2.2nM 的 Au 时即可被连续检测到。连续进行的高灵敏度采集首次允许提取渗透开始的滞后时间、稳态开始的滞后时间、扩散系数以及进入皮肤的 AuNPs 的流入数据。PET 可能成为开发含有纳米粒子的药物和化妆品局部制剂的极具价值的工具。
