Department of Autoimmunity, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Bioconjug Chem. 2010 Jan;21(1):93-101. doi: 10.1021/bc900311h.
This article describes the use of a fluorescent nanoprobe as a functional biomarker for the identification of increased vascular permeability in cancer/arthritis disease models. Synthesis of the fluorescent nanoprobe was achieved by passive loading of a fluorophore inside the nanoparticle using thin film hydration method. The outer layer of the nanoprobe was decorated with poly(ethylene glycol) arms to increase the bioavailability of the fluorophore. Stability studies of the nanoprobe showed that the particles were stable up to 70 days. The uptake and internalization of the fluorescent nanoprobe inside target cells was confirmed by fluorescence microscopy studies. Co-localization of the probe with the target tissue in vivo was unambiguously identified using intravital microscopy. Results from in vivo imaging studies showed that the particles had a long half-life in the circulation and passively targeted tumor or arthritic tissue. The increased and specific uptake of the fluorescent nanoprobe in tumor/arthritic tissue is attributed to an enhanced permeation and retention (EPR) effect. Use of an optical method to validate anti-inflammatory drugs in an arthritis disease model is demonstrated in this study. In general, this methodology could be used for detection of leaky vasculature in different pathological states.
本文描述了一种荧光纳米探针在癌症/关节炎疾病模型中作为增加血管通透性的功能生物标志物的应用。通过薄膜水化法将荧光团被动装载到纳米颗粒内部来合成荧光纳米探针。纳米探针的外层用聚乙二醇(PEG)臂进行修饰,以增加荧光团的生物利用度。纳米探针的稳定性研究表明,颗粒在 70 天内是稳定的。通过荧光显微镜研究证实了荧光纳米探针在靶细胞内的摄取和内化。利用活体显微镜明确鉴定了探针与目标组织在体内的共定位。体内成像研究结果表明,颗粒在循环中有很长的半衰期,并被动靶向肿瘤或关节炎组织。荧光纳米探针在肿瘤/关节炎组织中的高摄取和特异性摄取归因于增强的渗透和保留(EPR)效应。本研究中展示了使用光学方法在关节炎疾病模型中验证抗炎药物的效果。总的来说,这种方法可用于检测不同病理状态下的渗漏血管。