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Photouncaging nanoparticles for MRI and fluorescence imaging in vitro and in vivo

机译:用于体内和体外MRI和荧光成像的光致松解纳米颗粒

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Multimodal and multifunctional nanomaterials are promising candidates for bioimaging and therapeutic applications in the nanomedicine settings. Here we report the preparation of photouncaging nanoparticles with fluorescence and magnetic modalities and evaluation of their potentials for in vitro and in vivo bioimaging. Photoactivation of such bimodal nanoparticles prepared using photouncaging ligands, CdSe/ZnS quantum dots, and super paramagnetic iron oxide nanoparticles results in the systematic uncaging of the particles, which is correlated with continuous changes in the absorption, mass and NMR spectra of the ligands. Fluorescence and magnetic components of the bimodal nanoparticles are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and elemental analyses using energy dispersive X-ray (EDX) spectroscopy and X-ray photoelectron spectroscopy (XPS). Bioconjugation of the nanoparticles with peptide hormones renders them with biocompatibility and efficient intracellular transport as seen in the fluorescence and MRI images of mouse melanoma cells (B16) or human lung epithelial adenocarcinoma cells (H1650). Biocompatibility of the nanoparticles is evaluated using MTT cytotoxicity assays, which show cell viability over 90%. Further, we combine MRI and NIR fluorescence imaging in C57BL/6 (B6) mice subcutaneously or intravenously injected with the photouncaging nanoparticles and follow the in vivo fate of the nanoparticles. Interestingly, the intravenously injected nanoparticles initially accumulate in the liver within 30 min post injection and subsequently clear by the renal excretion within 48 h as seen in the time-dependent MRI and fluorescence images of the liver, urinary bladder, and urine samples. Photouncaging ligands such as the ones reported in this article are promising candidates for not only the site-specific delivery of nanomaterials-based contrast agents and drugs but also the systematic uncaging and renal clearance of nanomaterials after the desired in vivo application.
机译:多峰和多功能纳米材料是在纳米医学环境中生物成像和治疗应用的有前途的候选者。在这里,我们报告制备具有荧光和磁性模态的光致发射纳米粒子,并评估其体外和体内生物成像的潜力。使用光解开配体,CdSe / ZnS量子点和超顺磁性氧化铁纳米粒子制备的这种双峰纳米粒子的光活化导致粒子的系统解开,这与配体的吸收,质量和NMR光谱的连续变化相关。使用扫描电子显微镜(SEM),透射电子显微镜(TEM)和使用能量色散X射线(EDX)光谱和X射线光电子能谱(XPS)的元素分析来表征双峰纳米粒子的荧光和磁性成分。纳米颗粒与肽激素的生物共轭使其具有生物相容性和有效的细胞内转运能力,如小鼠黑素瘤细胞(B16)或人肺上皮腺癌细胞(H1650)的荧光和MRI图像所示。使用MTT细胞毒性测定法评估纳米颗粒的生物相容性,该测定法显示细胞活力超过90%。此外,我们在皮下注射或静脉注射光致开裂纳米粒子的C57BL / 6(B6)小鼠中,将MRI和NIR荧光成像相结合,并追踪纳米粒子的体内命运。有趣的是,静脉内注射的纳米颗粒最初在注射后30分钟内累积在肝脏中,随后在48小时内通过肾脏排泄而被清除,这在肝脏,膀胱和尿液样本的时间依赖性MRI和荧光图像中可见。像本文报道的那些那样的光解开配体不仅有望用于基于纳米材料的造影剂和药物的定点递送,而且有望在体内应用后纳米材料的系统化解开和肾脏清除。

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