Chen Hongyu, Wang Fenglin, Moore Thomas, Qi Bin, Sulejmanovic Dino, Hwu Shiou-Jyh, Mefford O Thompson, Alexis Frank, Anker Jeffrey N
Department of Chemistry, Department of BioEngineering, Center for Optical Materials Science and Engineering Technologies (COMSET), and Institute of Environmental Toxicology (CU-ENTOX); Clemson University, Clemson, SC, 29634, USA. Tel:+1-864-656-1726.
Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA.
J Mater Chem B. 2017;5(27):5412-5424. doi: 10.1039/C7TB01289F. Epub 2017 Jun 13.
Nanophosphors are promising contrast agents for deep tissue optical imaging applications because they can be excited by X-ray and near infrared light that penetrates deeply through tissue and generates almost no autofluorescence background in the tissue. For these bioimaging applications, the nanophosophors should ideally be small, monodispersed and brightly luminescent. However, most methods used to improve luminescence yield by annealing the particles to reduce crystal and surface defects (e.g. using flux or sintering agents) also cause particle fusion or require multiple component core-shell structures. Here, we report a novel method to prepare bright, uniformly sized X-ray nanophosphors (GdOS:Eu or Tb) and upconversion nanophosphors (YOS: Yb/Er, or Yb/Tm) with large crystal domain size without causing aggregation. A core-shell nanoparticle is formed, with NaF only in the core. We observe that increasing the NaF sintering agent concentration up to 7.6 mol% increases both crystal domain size and luminescence intensity (up to 40% of commercial microphosphors) without affecting the physical particticle diameter. Above 7.6 mol%, particle fusion is observed. The annealing is insensitive to the cation (Na or K) but varies strongly with anion, with F>Cl>CO>Br>I. The luminescence depends strongly on crystal domain size. The data agree reasonably well with a simple domain surface quenching model, although the size-dependence suggests additional quenching mechanisms within small domains. The prepared bright nanophosphors were subsequently functionalized with PEG-folic acid to target MCF-7 breast cancer cells which overexpress folic acid receptors. Both X-ray and upconversion nanophosphors provided low background and bright luminescence which was imaged through 1 cm chicken breast tissue at a low dose of nanophosphors 200 µL (0.1 mg/mL). We anticipate these highly monodispersed and bright X-ray and upconversion nanophosphors will have significant potential for tumor targeted imaging.
纳米磷光体是用于深层组织光学成像应用的有前景的造影剂，因为它们可以被X射线和近红外光激发，这些光能够深入穿透组织，并且在组织中几乎不产生自发荧光背景。对于这些生物成像应用，理想的纳米磷光体应该体积小、单分散且发光明亮。然而，大多数通过对颗粒进行退火以减少晶体和表面缺陷来提高发光产率的方法（例如使用助熔剂或烧结剂）也会导致颗粒融合，或者需要多组分核壳结构。在此，我们报告了一种制备具有大晶畴尺寸且不引起聚集的明亮、尺寸均匀的X射线纳米磷光体（GdOS:Eu或Tb）和上转换纳米磷光体（YOS:Yb/Er或Yb/Tm）的新方法。形成了一种核壳纳米颗粒，仅在核中含有NaF。我们观察到，将NaF烧结剂浓度提高到7.6 mol%，在不影响物理颗粒直径的情况下，会增加晶畴尺寸和发光强度（高达商业微磷光体的40%）。高于7.6 mol%时，会观察到颗粒融合。退火对阳离子（Na或K）不敏感，但对阴离子变化强烈，F>Cl>CO>Br>I。发光强烈依赖于晶畴尺寸。尽管尺寸依赖性表明在小晶畴内存在额外的猝灭机制，但这些数据与一个简单的畴表面猝灭模型相当吻合。随后，将制备得到的明亮纳米磷光体用聚乙二醇 - 叶酸进行功能化，以靶向过表达叶酸受体的MCF - 7乳腺癌细胞。X射线和上转换纳米磷光体都提供了低背景和明亮的发光，在低剂量的200 μL纳米磷光体（0.1 mg/mL）下通过1 cm厚的鸡胸组织成像。我们预计这些高度单分散且明亮发光的X射线和上转换纳米磷光体在肿瘤靶向成像方面将具有巨大潜力。
