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用于靶向多功能药物递送系统的透明质酸共轭FeO@CeO复合纳米颗粒的合成

Synthesis of Hyaluronic Acid-Conjugated FeO@CeO Composite Nanoparticles for a Target-Oriented Multifunctional Drug Delivery System.

作者信息

Lee Chang Ryong, Kim Gun Gyun, Park Sung Bum, Kim Sang Wook

机构信息

Department of Advanced Materials Chemistry, Dongguk University, Gyeongju 38066, Korea.

Department of Safety Engineering, Dongguk University, Gyeongju 38066, Korea.

出版信息

Micromachines (Basel). 2021 Aug 26;12(9):1018. doi: 10.3390/mi12091018.

DOI:10.3390/mi12091018
PMID:34577662
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8466504/
Abstract

This study is based on the principle that superparamagnetic iron oxide nanoparticles (FeO) can be used to target a specific area given that their magnetic properties emerge when an external magnetic field is applied. Cerium oxide (CeO), which causes oxidative stress by generating reactive oxygen species (ROS) in the environment of tumor cells, was synthesized on the surface of superparamagnetic iron oxide nanoparticles to produce nanoparticles that selectively kill cancer cells. In addition, hyaluronic acid (HA) was coated on the cerium's surface to target CD44-overexpressing tumor cells, and Zr was chelated on the FeO@CeO surface to show the usefulness of labeling the radioisotope Zr (T1/2 = 3.3 d). The synthesis of FeO@CeO was confirmed by Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Field Emission-Transmission Electron Microscope (FE-TEM). The coating of HA was confirmed by FT-IR, X-ray Photoelectron. Spectroscopy (XPS), FE-TEM, Energy-Dispersive X-ray Spectroscopy (EDS) and Thermogravimetric Analysis (TGA)/Differential Scanning Calorimetry (DSC). The sizes of the prepared nanoparticles were confirmed through FE-TEM and Field Emission-Scanning Electron (FE-SEM) (sizes of 15 to 30 nm), and it was confirmed that Zr was introduced onto the surface of the nanoparticles using EDS. The particle size of the dispersed material was limited through Dynamic Light Scattering (DLS) to about 148 nm in aqueous solution, which was suitable for the (enhanced permeation and retention) EPR effect. It was confirmed that the HA-coated nanoparticles have good dispersibility. Finally, a cytotoxicity evaluation confirmed the ability of CeO to generate ROS and target the delivery of HA. In conclusion, FeO@CeO can effectively inhibit cancer cells through the activity of cerium oxide in the body when synthesized in nano-sized superparamagnetic coral iron that has magnetic properties. Subsequently, by labeling the radioactive isotope Zr, it is possible to create a theranostic drug delivery system that can be used for cancer diagnosis.

摘要

本研究基于这样一个原理：超顺磁性氧化铁纳米颗粒（FeO）在施加外部磁场时会表现出磁性，因此可用于靶向特定区域。氧化铈（CeO）在肿瘤细胞环境中通过产生活性氧（ROS）引起氧化应激，将其合成在超顺磁性氧化铁纳米颗粒表面，以制备能选择性杀死癌细胞的纳米颗粒。此外，在铈的表面包覆透明质酸（HA）以靶向CD44过表达的肿瘤细胞，并在FeO@CeO表面螯合Zr以展示标记放射性同位素Zr（半衰期T1/2 = 3.3天）的效用。通过傅里叶变换红外光谱（FT-IR）、X射线衍射（XRD）和场发射透射电子显微镜（FE-TEM）证实了FeO@CeO的合成。通过FT-IR、X射线光电子能谱（XPS）、FE-TEM、能量色散X射线光谱（EDS）和热重分析（TGA）/差示扫描量热法（DSC）证实了HA的包覆。通过FE-TEM和场发射扫描电子显微镜（FE-SEM）确定了所制备纳米颗粒的尺寸（尺寸为15至30纳米），并使用EDS证实Zr被引入到纳米颗粒表面。通过动态光散射（DLS）将分散材料的粒径限制在水溶液中约148纳米，这适用于（增强渗透和滞留）EPR效应。证实了HA包覆的纳米颗粒具有良好的分散性。最后，细胞毒性评估证实了CeO产生活性氧并靶向递送HA的能力。总之，当在具有磁性的纳米级超顺磁性珊瑚铁中合成时，FeO@CeO可通过体内氧化铈的活性有效抑制癌细胞。随后，通过标记放射性同位素Zr，有可能创建一种可用于癌症诊断的治疗诊断药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/d24dfbb6f32d/micromachines-12-01018-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/b21a5743c9a2/micromachines-12-01018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/86f9c15482ab/micromachines-12-01018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/535a6a2fe901/micromachines-12-01018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/5e02128340eb/micromachines-12-01018-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/b8ad53ec3954/micromachines-12-01018-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/64a606088f7b/micromachines-12-01018-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/79f8c8929117/micromachines-12-01018-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/d24dfbb6f32d/micromachines-12-01018-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/b21a5743c9a2/micromachines-12-01018-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/86f9c15482ab/micromachines-12-01018-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/535a6a2fe901/micromachines-12-01018-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/5e02128340eb/micromachines-12-01018-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/b8ad53ec3954/micromachines-12-01018-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/64a606088f7b/micromachines-12-01018-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/79f8c8929117/micromachines-12-01018-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/482c/8466504/d24dfbb6f32d/micromachines-12-01018-g008.jpg

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引用本文的文献

[1]
Excipients for Cerium Dioxide Nanoparticle Stabilization in the Perspective of Biomedical Applications.

Molecules. 2025-3-8

[2]
A Study of Hyaluronic Acid's Theoretical Reactivity and of Magnetic Nanoparticles Capped with Hyaluronic Acid.

Materials (Basel). 2024-3-7

[3]
Hyaluronic Acid Modified Metal Nanoparticles and Their Derived Substituents for Cancer Therapy: A Review.

Pharmaceutics. 2023-6-12

本文引用的文献

[1]
Functionalized terahertz plasmonic metasensors: Femtomolar-level detection of SARS-CoV-2 spike proteins.

Biosens Bioelectron. 2021-4-1

[2]
Tumor Targeting Effect of Triphenylphosphonium Cations and Folic Acid Coated with Zr-89-Labeled Silica Nanoparticles.

Molecules. 2020-6-25

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J Nanobiotechnology. 2018-9-19

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