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微波辅助合成 FeO 稳定的 ZrO 纳米粒子-自由基清除、放射性标记及在兔体内的生物分布。

Microwave assisted synthesis of FeO stabilized ZrO nanoparticles - Free radical scavenging, radiolabeling and biodistribution in rabbits.

机构信息

Centre of Excellence in Solid State Physics, University of the Punjab, Lahore 54590, Pakistan.

Department of Cyclotron and Radiopharmaceutics, INMOL Cancer Hospital, Lahore 54600, Pakistan.

出版信息

Life Sci. 2021 Apr 15;271:119070. doi: 10.1016/j.lfs.2021.119070. Epub 2021 Jan 16.

Abstract

AIMS

In vivo biodistribution of radio labeled ZrO nanoparticles is addressed for better imaging, therapy and diagnosis. Nanoparticles are synthesized by microwave assisted sol-gel technique using FeO as a stabilizer. Antioxidant assay, hemolytic activity in human blood and biodistribution in rabbits was explored to study the therapeutical as well as in vivo targeted diagnostic applications of as synthesized nanoparticles.

MAIN METHODS

FeO stabilized zirconia nanoparticles are synthesized using microwave assisted sol-gel method. Microwave (MW) powers are varied in the range of 100 to 1000 W. As synthesized nanoparticles are evaluated using different characterizations such as X-ray diffractometer, scanning electron microscope, Raman spectroscopy, impedance analyzer, Vickers micro hardness indenter, FTIR, and UV-Vis spectroscopy. In vitro activity of synthesized nanoparticles is checked in freshly extracted human blood serum. To study biodistribution of FeO stabilized zirconia nanoparticles in rabbit, technetium-99 m was used for labeling purpose. The labeling efficacy and stability of labeled nanoparticles are also measured with instant thin layer chromatography (ITLC) method. Intravenous injection of Tc-FeO stabilized zirconia nanoparticles (0.2 ml), containing 110 MBq of radioactivity, is performed to study the biodistribution; nanoparticles are injected into the ear vein of animal (rabbit).

KEY FINDINGS

Zirconia (ZrO) nanoparticles (NPs) are stabilized using FeO that were prepared by means of microwave assisted sol-gel method. Crystallite size (20 nm) agrees well with the values required to stabilize tetragonal zirconia (t-ZrO). Volume shrinkage results in high value of hardness (1369). Dielectric constant values, compatible for biomedical application, are observed for tetragonally stabilized samples. Low value of hemolytic response is observed for FeO stabilized ZrO NPs. Tc radio labeled ZrO NPs proved to be potential candidate to study biodistribution. Biodistribution studies show stability of radiolabeled NPs in the original suspension as well as in blood serum. CT scan of rabbit is performed for several times to check the biodistribution of NPs with time and survival of rabbit. Results suggest that these NPs can also be used as targeted nanoparticles as well as variants of drug payload carrier.

SIGNIFICANCE

Results signify that FeO stabilized ZrO nanoparticles synthesized by microwave assisted sol-gel method may be considered as "all-rounder" nanoplatform and are safe enough to be used in diagnostic as well as therapeutic purposes.

摘要

目的

研究放射性标记的 ZrO 纳米粒子的体内生物分布,以实现更好的成像、治疗和诊断。纳米粒子通过微波辅助溶胶-凝胶技术合成,使用 FeO 作为稳定剂。通过抗氧化测定、人血溶血活性和兔体内分布研究,探索合成纳米粒子的治疗和体内靶向诊断应用。

方法

采用微波辅助溶胶-凝胶法合成 FeO 稳定的氧化锆纳米粒子。微波功率在 100 至 1000 W 的范围内变化。采用 X 射线衍射仪、扫描电子显微镜、拉曼光谱仪、阻抗分析仪、维氏硬度计、傅里叶变换红外光谱仪和紫外可见光谱仪等对合成的纳米粒子进行不同的表征。在新鲜提取的人血清中检查合成纳米粒子的体外活性。为了研究兔体内 FeO 稳定氧化锆纳米粒子的生物分布,使用锝-99m 进行标记。还使用即时薄层色谱 (ITLC) 法测量标记纳米粒子的标记效率和稳定性。通过静脉注射 Tc-FeO 稳定氧化锆纳米粒子(0.2 ml),其中含有 110 MBq 的放射性,研究生物分布;将纳米粒子注入动物(兔)的耳静脉。

结果

使用 FeO 稳定氧化锆(ZrO)纳米粒子(NPs),通过微波辅助溶胶-凝胶法制备。纳米粒子的晶粒尺寸(20nm)与稳定四方氧化锆(t-ZrO)所需的尺寸相符。体积收缩导致硬度值较高(1369)。观察到具有生物医学应用兼容性的四方稳定样品的介电常数值。FeO 稳定的 ZrO NPs 的溶血反应值较低。Tc 放射性标记的 ZrO NPs 被证明是研究生物分布的潜在候选物。生物分布研究表明,标记的 NPs 在原始悬浮液中和在血清中都具有稳定性。对兔子进行多次 CT 扫描,以检查 NPs 随时间和兔子存活的生物分布。结果表明,这些 NPs 也可用作靶向纳米颗粒和药物有效载荷载体的变体。

意义

结果表明,通过微波辅助溶胶-凝胶法合成的 FeO 稳定的 ZrO 纳米粒子可以被认为是一种“全能”纳米平台,并且足够安全,可以用于诊断和治疗目的。

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