Cluster for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, 2052 NSW, Australia.
Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, 2006 NSW, Australia.
ACS Appl Mater Interfaces. 2021 Apr 14;13(14):16142-16154. doi: 10.1021/acsami.1c01922. Epub 2021 Mar 31.
The ability of upconversion nanoparticles (UCNPs) to convert low-energy near-infrared (NIR) light into high-energy visible-ultraviolet light has resulted in their development as novel contrast agents for biomedical imaging. However, UCNPs often succumb to poor colloidal stability in aqueous media, which can be conquered by decorating the nanoparticle surface with polymers. The polymer cloak, therefore, plays an instrumental role in ensuring good stability in biological media. This study aims to understand the relationship between the length and grafting density of the polymer shell on the physicochemical and biological properties of these core-shell UCNPs. Poly(ethylene glycol) methyl ether methacrylate block ethylene glycol methacrylate phosphate (PPEGMEMA--PEGMP) with different numbers of PEGMEMA repeating units (26, 38, and 80) was prepared and attached to the UCNPs the phosphate ligand of the poly(ethylene glycol methacrylate phosphate) (PEGMP) block at different polymer densities. The and protein corona, cellular uptake in two-dimensional (2D) monolayer and three-dimensional (3D) multicellular tumor spheroid (MCTS) models, and biodistribution in mice were evaluated. Furthermore, the photoluminescence of single-polymer-coated UCNPs was compared in solid state and cancer cells using laser scanning confocal microscopy (LSCM). Our results showed that the bioactivity and luminescence properties are chain length and grafting density dependent. The UCNPs coated with the longest PPEGMEMA chain, grafted at low brush density, were able to reduce the formation of the protein corona and , while these UCNPs also showed the brightest upconversion luminescence in the solid state. Moreover, these particular polymer-coated UCNPs showed enhanced cellular uptake, extended blood circulation time, and more accumulation in the liver, brain, and heart.
上转换纳米粒子（UCNPs）将低能量近红外（NIR）光转化为高能可见-紫外光的能力使其成为生物医学成像的新型对比剂。然而，UCNPs 在水介质中往往表现出较差的胶体稳定性，这可以通过在纳米粒子表面修饰聚合物来克服。因此，聚合物“斗篷”在确保在生物介质中良好的稳定性方面起着重要作用。本研究旨在了解聚合物壳的长度和接枝密度与这些核壳 UCNPs 的物理化学和生物学性质之间的关系。合成了不同数目的聚乙二醇甲基醚甲基丙烯酸酯嵌段聚乙二醇甲基丙烯酸酯磷酸酯（PPEGMEMA-PEGMP）的聚（乙二醇甲基醚甲基丙烯酸酯）（PPEGMEMA）重复单元（26、38 和 80），并将其附着到 UCNPs 上，磷酸酯配体聚（乙二醇甲基丙烯酸酯磷酸酯）（PEGMP）块以不同的聚合物密度。评估了 和 蛋白冠、二维（2D）单层和三维（3D）多细胞肿瘤球体（MCTS）模型中的细胞摄取以及在小鼠中的 生物分布。此外，使用激光扫描共聚焦显微镜（LSCM）比较了单聚合物包覆 UCNPs 在固态和癌细胞中的光致发光。我们的结果表明，生物活性和发光性能取决于链长和接枝密度。用最长的 PPEGMEMA 链涂覆、以低刷密度接枝的 UCNPs 能够减少蛋白冠的形成 和 ，同时这些 UCNPs 在固态下也表现出最亮的上转换发光。此外，这些特殊的聚合物包覆 UCNPs 显示出增强的细胞摄取、延长的 血液循环时间以及在肝脏、大脑和心脏中的更多积累。
