Water-Dispersible Ferrimagnetic Iron Oxide Nanocubes with Extremely High <i>r</i><sub>2</sub> Relaxivity for Highly Sensitive in Vivo MRI of Tumors

Lee, Jun Young; Choi, Yoonseok; Lee, Youjin; Park, Mi-Hyun; Moon, Woo Kyung; Choi, Seung Hong; Hyeon, Taeghwan

doi:10.1021/nl3010308

Cited by 274 publications

(277 citation statements)

References 51 publications

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“…The influence of different synthetic parameters 49 on the structural characteristics of the CNCs were carefully examined in order to attain a significant degree of size/shape homogeneity. 57 …”

Section: C1 Morphology and Crystal Structurementioning

confidence: 99%

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

et al. 2014

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Section: C1 Morphology and Crystal Structurementioning

confidence: 99%

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

et al. 2014

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“…Interestingly, 22 nm ferrimagnetic iron oxide nanocubes (NCs) formed closely at superparamagnetic range could be utilized as MRI or effective hyperthermia agents by encapsulating them in polymers that minimize the aggregation of ferrimagnetic iron oxides. [10][11][12] Unlike superparamagnetic nanoparticles, these ferrimagnetic NCs are difficult to maintain in a dispersed state by themselves. However, as we describe in this paper, multiple 22 nm ferrimagnetic NCs can be contained within a larger chitosan-coated nanoparticle that can be maintained in a dispersed state.…”

Section: Introductionmentioning

confidence: 99%

“…The ferrimagnetic iron oxide NCs show high MRI contrast and hyperthermia. 10,13 However, ferrimagnetic iron oxide NCs are not easy to use in biological applications due to magnetic memory after exposure to an external magnetic field. Magnetic memory leads the iron oxide particles to cluster quickly, which could boost precipitation of the particles in biological conditions.…”

Section: Introductionmentioning

confidence: 99%

Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

Key¹,

Dhawan²,

Cooper³

et al. 2016

IJN

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While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs. Finely altering the nano-scale properties can dramatically change the biodistribution and tumor accumulation of nanoparticles in the body. In this study, we engineered multimodal nanoparticles for both MRI, by using ferrimagnetic nanocubes (NCs), and near infrared fluorescence imaging, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging.

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“…5 SPIONs are known as negative (or T 2 -weighted) MRI contrast agents (CAs), which decrease the signal intensity of the hydrogen nuclei within the tissues/regions where they are delivered. 24 The main advantage of SPIONs as MRI CAs is their high sensitivity, resulting in signicant contrast enhancement in MR images. 25 There has been great interest in synthesizing novel CAs and studying the inuence of microstructural parameters such as the magnetic core size on the MRI contrast efficiency.…”

mentioning

confidence: 99%

Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles

et al. 2013

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Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood.Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. 1 H relaxometry was used to obtain the longitudinal, r 1 , and transverse, r 2 , relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at n ¼ 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings.It is well-recognized that the surface of nanoparticles (NPs) is covered by biomolecules (proteins, sugars and lipids) upon coming into contact with biological systems, resulting in the formation of a protein "corona" that is strongly associated with the NPs' surface and that denes how living organisms (e.g. cells) "see" the NPs in a biological milieu. 1-5 According to previous reports, the cell "sees" a nano-system in which the NPs are covered by a "hard" corona of slowly exchanging proteins with a surrounding "so" corona consisting of weakly interacting and rapidly exchanging proteins. 6 The composition of the protein corona (PC) is highly dependent on the physicochemical properties of the NPs such as their size, composition, and surface characteristics. 7 Superparamagnetic iron oxide nanoparticles (SPIONs) have been recognized as very promising nanosystems with good biocompatibility 8,9 and high potential to be used for diagnosis and therapy simultaneou...

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Water-Dispersible Ferrimagnetic Iron Oxide Nanocubes with Extremely High r₂ Relaxivity for Highly Sensitive in Vivo MRI of Tumors

Cited by 274 publications

References 51 publications

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles

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Water-Dispersible Ferrimagnetic Iron Oxide Nanocubes with Extremely High r2 Relaxivity for Highly Sensitive in Vivo MRI of Tumors

Cited by 274 publications

References 51 publications

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

Colloidal assemblies of oriented maghemite nanocrystals and their NMR relaxometric properties

Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles

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Water-Dispersible Ferrimagnetic Iron Oxide Nanocubes with Extremely High r₂ Relaxivity for Highly Sensitive in Vivo MRI of Tumors