The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways

Abstract

In recent years, iron oxide nanoparticles (IONPs) have been applied widely to biomedical fields. However, the relationship between the physicochemical properties of IONPs and their biological behavior is not fully understood yet. We prepared 3-methacryloxypropyltrimethoxysilane (MPS)-coated IONPs, which have a neutral hydrophobic surface, and compared their biological behavior to that of Resovist (ferucarbotran), a commercialized IONP formulation modified with carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial cells (HAoECs) was higher than ferucarbotran uptake, indicating that the neutral hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through the plasma membrane. However, the signaling pathways activated by MPS-IONPs and ferucarbotran were comparable, suggesting that surface charge is not a key factor for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs accumulated for longer periods in tissues than hydrophilic ferucarbotran. These findings could enlarge our understanding of NP behavior for advanced applications in the biomedical field.

Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety

“… 34 The spectrum of ferucarbotran differs in this respect in the C-O-C vibrational region, and in the appearance of another peak at 1591 cm −1 , representing the carboxyl functionalization of its dextran shell. 41 Typical peaks of the polyglucose sorbitol carboxymethyl ether coating were detectable in the spectrum of ferumoxytol. 42 For 3T MRI, R 1 , R 2 and R 2 * relaxation rates were measured using different MRI protocols to determine the contrast agent relaxivity values r 1 , r 2 and r 2 * as a measure of in vitro MRI contrast efficiency (see Figure 1C–E ).…”

“…While the coating of SPION Dex consists of cross-linked dextran, the FTIR spectrum of ferucarbotran showed a less smeared C-O-C vibrational region, indicating the absence of cross-linking, and an appearance of another peak at 1591 cm −1 , representing the carboxyl functionalization of its dextran shell, that contributes to its high surface charge. 41 Also in ferumoxytol, carboxyl groups are responsible for the high negative surface charge. 42 Despite strong differences in surface charge, all three nanoparticle formulations were characterized with a good colloidal stability in aqueous media and blood, which can be attributed to good electrosteric or steric stabilization due to their respective carbohydrate coating.…”

<p>Bombesin-functionalized superparamagnetic iron oxide nanoparticles for dual-modality MR/NIRFI in mouse models of breast cancer</p>

“…In the present study, we developed a novel dual-modality MR/NIRFI nanomicelle by entrapping SPIO nanoparticles into DSPE-PEG5k micelles to which Cy5 and Bom were conjugated. Physical characterization showed that the near-neutral charged nanosized micelles were in the optimum range for enhancing cellular accumulation and biodistribution 38,39. The morphology of nanomicelles also plays a critical role in their cellular fate; spherical nanomicelles, as observed by TEM, show more efficient internalization by tumor cells 40,41…”

A guide to the design of magnetic particle imaging tracers for biomedical applications

“…47,50,51,53 For example, Resovist has been designed on the basis of polycrystalline iron oxide MNPs consisting of multiple single crystals coated with carboxydextran with a hydrodynamic size of more than 60 nm in diameter. 54,55 When a weak external field is applied to polycrystalline MNPs, the individual magnetic moment vectors cannot linearly sum due to the availability of antiphase boundaries, resulting in a lower M sat value. 25 Additionally, only MNPs with a diameter of about 30 nm play a significant role in the overall signal generation according to Langevin-theory, which means that only 3% of the total iron mass of the Resovist® solution contributes to the MPI signal.…”