Lu Chao, Ouyang Jianying, Zhang Jin
Department of Chemical and Biochemical Engineering, University of Western Ontario, London, ON, N6A 5B9, Canada.
Quantum and Nanotechnologies Research Center, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, K1A 0R6, Canada.
Discov Nano. 2024 Nov 12;19(1):181. doi: 10.1186/s11671-024-04139-w.
Upconversion nanoparticles (UCNPs), capable of converting near-infrared (NIR) light into high-energy emission, hold significant promise for bioimaging applications. However, the presence of tissue barriers poses a challenge to the effective delivery of nanoparticles (NPs) to target organs. In this study, we demonstrate the core-shell UCNPs modified with cationic biopolymer, i.e., N, N-trimethyl chitosan (TMC), can overcome endothelial barriers. The core-shell UCNP is composed of NaGdF: Yb,Tm (16.7 ± 2.7 nm) as core materials and silica (SiO) shell. The average particle size of UCNPs@SiO is estimated at 26.1 ± 3.7 nm. X-ray diffraction (XRD), transmission electron microscopy (TEM) and element mapping shows the formation of hexagonal crystal structure of β-NaGdF and elements doping. The surface of UCNPs@SiO has been modified with poly(ethylene glycol) (PEG) to enhance water dispersibility and colloidal stability, and further modified with TMC with the zeta potential increasing from -2.1 ± 0.96 mV to 26.9 ± 12.6 mV. No significant toxic effect is imposed to HUVECs when the cells are treated with core-shell UCNPs with surface modification up to 250 µg/mL. The transport ability of the core-shell UCNPs has been evaluated by using the in vitro endothelial barrier model. Transepithelial electrical resistance (TEER) and immunofluorescence staining of tight junction proteins have been employed to verify the integrity of the in vitro endothelial barrier model. The results indicate that the transport percentage of the UCNPs@SiO with PEG and TMC through the model is up to 4.56%, which is twice higher than that of the UCNPs@SiO with PEG but without TMC and six times that of the UCNPs@SiO.
上转换纳米粒子（UCNPs）能够将近红外（NIR）光转化为高能发射，在生物成像应用中具有巨大潜力。然而，组织屏障的存在对纳米粒子（NPs）有效递送至靶器官构成了挑战。在本研究中，我们证明了用阳离子生物聚合物即N，N-三甲基壳聚糖（TMC）修饰的核壳UCNPs能够克服内皮屏障。核壳UCNP由NaGdF:Yb,Tm（16.7±2.7 nm）作为核心材料和二氧化硅（SiO）壳组成。UCNPs@SiO的平均粒径估计为26.1±3.7 nm。X射线衍射（XRD）、透射电子显微镜（TEM）和元素映射显示了β-NaGdF的六方晶体结构的形成和元素掺杂。UCNPs@SiO的表面已用聚乙二醇（PEG）进行修饰以提高水分散性和胶体稳定性，并进一步用TMC进行修饰，其zeta电位从-2.1±0.96 mV增加到26.9±12.6 mV。当用表面修饰的核壳UCNPs处理细胞至250 μg/mL时，对人脐静脉内皮细胞（HUVECs）没有显著的毒性作用。通过使用体外内皮屏障模型评估了核壳UCNPs的转运能力。采用跨上皮电阻（TEER）和紧密连接蛋白的免疫荧光染色来验证体外内皮屏障模型的完整性。结果表明，带有PEG和TMC的UCNPs@SiO通过该模型的转运百分比高达4.56%，这是不带TMC但带有PEG的UCNPs@SiO的两倍，是UCNPs@SiO的六倍。
