Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors

Larsen, Elfinn; Nielsen, Thomas; Wittenborn, Thomas; Birkedal, Henrik; Vorup-Jensen, Thomas; Jakobsen, Mogens; Østergaard, Leif; Horsman, Michael R.; Besenbacher, Flemming; Howard, Kenneth A.; Kjems, Jørgen

doi:10.1021/nn900330m

Cited by 237 publications

(185 citation statements)

References 24 publications

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“…Larsen et al found that the uptake of PEG-SPIOs was eightfold higher when the SPIO size was increased from 20 nm to 40 nm. 18 Tabata and Ikada showed that macrophage uptake is increased with microsphere sizes up to 1.5 µm in diameter. 19 Our results show that SPIO uptake was not further increased if particle sizes larger than 60 nm were reached.…”

Section: Figurementioning

confidence: 99%

Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles

Roohi

Lohrke²,

Ide³

et al. 2012

IJN

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Purpose: Magnetic resonance imaging (MRI), one of the most powerful imaging techniques available, usually requires the use of an on-demand designed contrast agent to fully exploit its potential. The blood kinetics of the contrast agent represent an important factor that needs to be considered depending on the objective of the medical examination. For particulate contrast agents, such as superparamagnetic iron oxide nanoparticles (SPIOs), the key parameters are particle size and characteristics of the coating material. In this study we analyzed the effect of these two properties independently and systematically on the magnetic behavior and blood half-life of SPIOs. Methods: Eleven different SPIOs were synthesized for this study. In the first set (a), seven carboxydextran (CDX)-coated SPIOs of different sizes (19-86 nm) were obtained by fractionating a broadly size-distributed CDX-SPIO. The second set (b) contained three SPIOs of identical size (50 nm) that were stabilized with different coating materials, polyacrylic acid (PAA), polyethylene glycol, and starch. Furthermore, small PAA-SPIOs (20 nm) were synthesized to gain a global insight into the effects of particle size vs coating characteristics. Saturation magnetization and proton relaxivity were determined to represent the magnetic and imaging properties. The blood half-life was analyzed in rats using MRI, time-domain nuclear magnetic resonance, and inductively coupled plasma optical emission spectrometry. Results: By changing the particle size without modifying any other parameters, the relaxivity r 2 increased with increasing mean particle diameter. However, the blood half-life was shorter for larger particles. The effect of the coating material on magnetic properties was less pronounced, but it had a strong influence on blood kinetics depending on the ionic character of the coating material. Conclusion:In this report we systematically demonstrated that both particle size and coating material influence blood kinetics and magnetic properties of SPIO independently. These data provide key information for the selection of a contrast agent for a defined application and are additionally valuable for other nano areas, such as hyperthermia, drug delivery, and nanotoxicology.

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Section: Figurementioning

confidence: 99%

Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles

Roohi

Lohrke²,

Ide³

et al. 2012

IJN

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“…The peak at 1,096 cm -1 most likely derives from the C-O stretching vibration of ether groups, the peaks at 947 cm -1 can be assigned to C-H rocking in the PEG chain and appearance of two new bands around 2,927 and 2,851 cm -1 belonging to C-H stretching vibration implies the presence of PEG chain in the structure of modified MNPs. The peak at 1,020 cm -1 can be assigned to Si-O stretch vibration on the surface of Fe 3 O 4 nanoparticles [23].…”

Section: Synthesis Of Magnetite Nanoparticles (Mnps)mentioning

confidence: 99%

“…Carlos Rinaldi and co-workers [22] synthesized stable colloidal dispersions of monodisperse magnetic nanoparticles in water by the thermal decomposition method, and exchanging the oleic acid molecules on the surface of the particles for PEG-silane chains. Larsen and co-workers [23] prepared silane-PEG-coated MNPs using a simple synthesis method based on the use of biocompatible silane-PEG as a coating agent.…”

Section: Introductionmentioning

confidence: 99%

A new procedure for preparation of polyethylene glycol-grafted magnetic iron oxide nanoparticles

Khoee

Kavand

2014

J Nanostruct Chem

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Magnetic iron oxide nanoparticles (MNPs) have been widely explored for use in biomedical applications. In the present study, iron oxide nanoparticles were connected to methoxy poly(ethylene glycol) (mPEG) via a new method. The mPEG was acrylated at first and Michael reaction was carried out between acrylated mPEG and 3-aminopropyl triethoxysilane as a coupling agent. The chemical structures of modified mPEG were characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance. In the next step, iron oxide nanoparticle was coupled with the above-mentioned adduct. Preparation of magnetic nanoparticles with average particle size of 20-30 nm was proved by scanning electron microscopy. The structure of mPEG grafted on the surface of MNPs was confirmed by FT-IR spectroscopy and thermal gravimetric analysis. The synthesized nanoparticles have the potential to be used in different biomedical applications.

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“…This can be improved through tumor targeting strategies that link contrast agents to a polymer or nanoparticle. Nanoparticles are well suited to act as tumor targeting vehicles because their in vivo behavior is determined by their design, and they are able to leak into and accumulate in tumors via the enhanced permeability and retention effect (3)(4)(5)(6)(7). Despite these advantages, several obstacles limit effective tumor detection with nanoparticle-based targeting strategies.…”

mentioning

confidence: 99%

In vivo assembly of nanoparticle components to improve targeted cancer imaging

Perrault

Chan

2010

Proc. Natl. Acad. Sci. U.S.A.

162

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Many small molecular anticancer agents are often ineffective at detecting or treating cancer due to their poor pharmacokinetics. Using nanoparticles as carriers can improve this because their large size reduces clearance and improves retention within tumors, but it also slows their rate of transfer from circulation into the tumor interstitium. Here, we demonstrate an alternative strategy whereby a molecular contrast agent and engineered nanoparticle undergo in vivo molecular assembly within tumors, combining the rapid influx of the smaller and high retention of the larger component. This strategy provided rapid tumor accumulation of a fluorescent contrast agent, 16-and 8-fold faster than fluorescently labeled macromolecule or nanoparticle controls achieved. Diagnostic sensitivity was 3.0 times that of a passively targeting nanoparticle, and this improvement was achieved 3 h after injection. The advantage of the in vivo assembly approach for targeting is rapid accumulation of small molecular agents in tumors, shorter circulation time requirements, possible systemic clearance while maintaining imaging sensitivity in the tumor, and nanoparticle anchors in tumors can be utilized to alter the pharmacokinetics of contrast agents, therapeutics, and other nanoparticles. This study demonstrates molecular assembly of nanoparticles within tumors, and provides a new basis for the future design of nanomaterials for medical applications. Determining the correct prognosis and therapeutic options for cancer requires accurate staging and surveillance of tumors. Current detection strategies typically combine sensitive imaging modalities with contrast agents (1, 2). Yet these approaches fail to detect lesions in many cases, typically because poor imaging contrast is achieved (2). This can be improved through tumor targeting strategies that link contrast agents to a polymer or nanoparticle. Nanoparticles are well suited to act as tumor targeting vehicles because their in vivo behavior is determined by their design, and they are able to leak into and accumulate in tumors via the enhanced permeability and retention effect (3-7). Despite these advantages, several obstacles limit effective tumor detection with nanoparticle-based targeting strategies. Passive targeting requires particles with large diameters, but this simultaneously restricts transport into tumors and accumulation occurs only after many hours in circulation (8-10). Actively targeting nanoparticle designs can achieve faster accumulation (11-13), but may not be appropriate for detecting lesions whose antigens are uncharacterized or are heterogeneous and therefore unreliable. Finally, nanoparticles have long circulation and persistence times in the body, raising potential concerns of diagnostic or therapeutic agent toxicity. It would therefore be advantageous to develop targeting strategies that can rapidly accumulate contrast agent into tumors without relying on antigen characterization and without causing long-term persistence in the body.The movement of nanoparticles th...

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Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors

Cited by 237 publications

References 24 publications

Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles

Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles

A new procedure for preparation of polyethylene glycol-grafted magnetic iron oxide nanoparticles

In vivo assembly of nanoparticle components to improve targeted cancer imaging

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