Iron Oxide Nanoparticles Are Less Toxic to Endothelial Cells When Coated With Dextran and Polyethylene Glycol

Author(s):  
Miao Yu ◽  
Vladimir Muzykantov ◽  
Alisa Morss Clyne

Iron oxide nanoparticles are of particular interest for drug delivery applications, since they can be targeted to a specific location using a magnetic field. We are interested in delivering drugs to atherosclerotic plaques via these nanoparticles. However, prior to using nanoparticles in vivo, they must be shown as relatively non-toxic to cells. We and others have shown that bare iron oxide nanoparticles are readily taken up by cells, where they catalyze production of highly toxic reactive oxygen species [1]. This oxidative stress disrupts the cell cytoskeleton, alters cell mechanics, and may change other critical cell functions. Iron oxide nanoparticles for in vivo biomedical applications are often coated with a polysaccharide (eg. dextran) or a polymer (eg. polyethylene glycol, PEG). Both the size and the surface coating of the nanoparticle play an important role in cell toxicity.

Author(s):  
Miao Yu ◽  
Alisa Morss Clyne

Iron oxide nanoparticles are of interest for drug delivery, since they can be targeted using a magnetic field. However, prior to using nanoparticles in vivo, they must be shown as relatively non-toxic to cells. We and others have shown that bare iron oxide nanoparticles are readily taken up by cells, where they catalyze production of highly toxic reactive oxygen species (ROS). This oxidative stress disrupts the cell cytoskeleton and alters cell mechanics. [1] Iron oxide nanoparticles under current development for in vivo biomedical applications are often coated with a polysaccharide (eg. dextran) or a polymer (eg. polyethylene glycol, PEG). Both the size and the surface coating of nanoparticle may play an important role in cell toxicity.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Shalini Sharma ◽  
Nisha Lamichhane ◽  
Parul ◽  
Tapas Sen ◽  
Indrajit Roy

The role and scope of functional inorganic nanoparticles in biomedical research is well established. Among these, iron oxide nanoparticles (IONPs) have gained maximum attention as they can provide targeting, imaging and therapeutic capabilities. Furthermore, incorporation of organic optical probes with IONPs can significantly enhance the scope and viability of their biomedical applications. Combination of two or more such applications renders multimodality in nanoparticles, which can be exploited to obtain synergistic benefits in disease detection and therapy viz theranostics, which is a key trait of nanoparticles for advanced biomedical applications. This review focuses on the use of IONPs conjugated with organic optical probe/s for multimodal diagnostic and therapeutic applications in vivo.


2021 ◽  
Vol 19 ◽  
pp. 228080002110147
Author(s):  
Chan Woo Kim ◽  
Byung-Hee Hwang ◽  
Hyeyoung Moon ◽  
Jongeun Kang ◽  
Eun-Hye Park ◽  
...  

Identification of a vulnerable atherosclerotic plaque before rupture is an unmet clinical need. Integrating nanomedicine with multimodal imaging has the potential to precisely detect biological processes in atherosclerosis. We synthesized silica-coated iron oxide nanoparticles (SIONs) coated with rhodamine B isothiocyanate and polyethylene glycol and investigated their feasibility in the detection of macrophages in inflamed atherosclerotic plaques of apolipoprotein E-deficient (ApoE−/−) mice via magnetic resonance (MR) and fluorescence reflectance (FR) imaging. In vitro cellular uptake of SIONs was assessed in macrophages using confocal laser scanning microscopy (CLSM). In vivo MR imaging was performed 24 h after SION injection via the tail vein in 26-week-old ApoE−/− mice fed a high-cholesterol diet (HCD). We also performed FR imaging of the extracted aortas from four different mice: two normal-diet-fed C57BL/6 mice injected with saline or 10 mg/kg SIONs and two HCD-fed ApoE−/− mice injected with 5 or 10 mg/kg SIONs. The harvested aortas were cryosectioned and stained with immunohistochemical staining. The CLSM images at 24 h after incubation showed efficient uptake of SIONs by macrophages, with no evidence of cytotoxicity. The in vivo and ex vivo MR and FR images demonstrated SION deposition in the atheroma. Upon immunohistochemical staining of the aorta, CLSM images revealed colocalization of macrophages and SIONs in the atherosclerotic plaque. These results demonstrate that polyethylene glycosylated SIONs could be a highly effective method to identify macrophage activity in atherosclerotic plaques as a multimodal imaging agent.


Materials ◽  
2019 ◽  
Vol 12 (14) ◽  
pp. 2218 ◽  
Author(s):  
Amalia Ruiz ◽  
Adán Alpízar ◽  
Lilianne Beola ◽  
Carmen Rubio ◽  
Helena Gavilán ◽  
...  

Superparamagnetic iron oxide nanoparticles are one of the most prominent agents used in theranostic applications, with MRI imaging the main application assessed. The biomolecular interface formed on the surface of a nanoparticle in a biological medium determines its behaviour in vitro and in vivo. In this study, we have compared the formation of the protein corona on highly monodisperse iron oxide nanoparticles with two different coatings, dimercaptosuccinic acid (DMSA), and after conjugation, with a bifunctional polyethylene glycol (PEG)-derived molecule (2000 Da) in the presence of Wistar rat plasma. The protein fingerprints around the nanoparticles were analysed in an extensive proteomic study. The results presented in this work indicate that the composition of the protein corona is very difficult to predict. Proteins from different functional categories—cell components, lipoproteins, complement, coagulation, immunoglobulins, enzymes and transport proteins—were identified in all samples with very small variability. Although both types of nanoparticles have similar amounts of bonded proteins, very slight differences in the composition of the corona might explain the variation observed in the uptake and biotransformation of these nanoparticles in Caco-2 and RAW 264.7 cells. Cytotoxicity was also studied using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Controlling nanoparticles’ reactivity to the biological environment by deciding on its surface functionalization may suggest new routes in the control of the biodistribution, biodegradation and clearance of multifunctional nanomedicines.


Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2113
Author(s):  
Matthew James ◽  
Richard A Revia ◽  
Zachary Stephen ◽  
Miqin Zhang

Research efforts into the production and application of iron oxide nanoparticles (IONPs) in recent decades have shown IONPs to be promising for a range of biomedical applications. Many synthesis techniques have been developed to produce high-quality IONPs that are safe for in vivo environments while also being able to perform useful biological functions. Among them, coprecipitation is the most commonly used method but has several limitations such as polydisperse IONPs, long synthesis times, and batch-to-batch variations. Recent efforts at addressing these limitations have led to the development of microfluidic devices that can make IONPs of much-improved quality. Here, we review recent advances in the development of microfluidic devices for the synthesis of IONPs by coprecipitation. We discuss the main architectures used in microfluidic device design and highlight the most prominent manufacturing methods and materials used to construct these microfluidic devices. Finally, we discuss the benefits that microfluidics can offer to the coprecipitation synthesis process including the ability to better control various synthesis parameters and produce IONPs with high production rates.


2015 ◽  
Vol 3 (18) ◽  
pp. 3730-3737 ◽  
Author(s):  
Chichong Lu ◽  
Min Kyu Park ◽  
Chenxin Lu ◽  
Young Haeng Lee ◽  
Kyu Yun Chai

A mussel-inspired poly(ethylene glycol)-grafted-chitooligosaccharide based multidentate ligand (ML) is designed for preparing robust biocompatible iron oxide nanoparticles. The successful in vivo MRI application confirmed their suitability for biomedical applications.


2017 ◽  
Vol 249 ◽  
pp. 192-212 ◽  
Author(s):  
Miroslava Nedyalkova ◽  
Borjana Donkova ◽  
Julia Romanova ◽  
George Tzvetkov ◽  
Sergio Madurga ◽  
...  

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