Abstract：
Upconversion nanoparticles (UCNPs) are materials that provide unique advantages for biomedical applications. There are constantly emerging customized UCNPs with varying compositions, coatings, and upconversion mechanisms. Cellular uptake is a key parameter for the biological application of UCNPs. Uptake experiments have yielded highly varying results, and correlating trends between cellular uptake with different types of UCNP coatings remains challenging. In this report, the impact of surface polymer coatings on the formation of protein coronas and subsequent cellular uptake of UCNPs by macrophages and cancer cells was investigated. Luminescence confocal microscopy and elemental analysis techniques were used to evaluate the different coatings for internalization within cells. Pathway inhibitors were used to unravel the specific internalization mechanisms of polymer-coated UCNPs. Coatings were chosen as the most promising for colloidal stability, conjugation chemistry, and biomedical applications. PIMA-PEG (poly(isobutylene-alt-maleic) anhydride with polyethylene glycol)-coated UCNPs were found to have low cytotoxicity, low uptake by macrophages (when compared with PEI, poly(ethylenimine)), and sufficient uptake by tumor cells for surface-loaded drug delivery applications. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) studies revealed that PIMA-coated NPs were preferentially internalized by the clathrin- and caveolar-independent pathways, with a preference for clathrin-mediated uptake at longer time points. PMAO-PEG (poly(maleic anhydride-alt-1-octadecene) with polyethylene glycol)-coated UCNPs were internalized by energy-dependent pathways, while PAA- (poly(acrylic acid)) and PEI-coated NPs were internalized by multifactorial mechanisms of internalization. The results indicate that copolymers of PIMA-PEG coatings on UCNPs were well suited for the next-generation of biomedical applications.
摘要：
上转换纳米颗粒(UCNP)是为生物医学应用提供独特优势的材料。有不断涌现的定制UNP，具有不同的组成，涂层,和上转换机制。细胞摄取是UCNPs生物应用的关键参数。摄取实验产生了高度不同的结果，与不同类型的UCNP涂层的细胞摄取之间的相关趋势仍然具有挑战性。在这份报告中,研究了表面聚合物涂层对巨噬细胞和癌细胞形成蛋白冠和随后细胞摄取UCNPs的影响.使用发光共聚焦显微镜和元素分析技术来评估不同涂层在细胞内的内化。通路抑制剂用于阐明聚合物包被的UCNP的特定内化机制。涂层被选为最有前途的胶体稳定性，共轭化学，和生物医学应用。发现PIMA-PEG（聚（异丁烯-alt-马来）酸酐与聚乙二醇）包被的UCNPs具有低细胞毒性，巨噬细胞的低摄取(与PEI相比，聚（乙烯亚胺），以及肿瘤细胞对表面负载药物递送应用的充分摄取。电感耦合等离子体发射光谱（ICP-OES）研究表明，PIMA涂层的NPs优先被不依赖笼状和小窝的途径内化，在更长的时间点优先考虑网格蛋白介导的摄取。PMAO-PEG（聚（马来酸酐-alt-1-十八碳烯）与聚乙二醇）涂覆的UCNP通过能量依赖性途径内化，而PAA-（聚（丙烯酸））和PEI涂层的NP通过多因子内化机制内化。结果表明，UCNP上的PIMA-PEG涂层共聚物非常适合下一代生物医学应用。
