Paramagnetic Mn₈Fe₄-co-Polystyrene Nanobeads as a Potential T₁–T₂ Multimodal Magnetic Resonance Imaging Contrast Agent with In Vivo Studies

Abstract

In developing a cluster-nanocarrier design, as a magnetic resonance imaging contrast agent, we have investigated the enhanced relaxivity of a manganese and iron-oxo cluster grafted within a porous polystyrene nanobead with increased relaxivity due to a higher surface area. The synthesis of the cluster-nanocarrier for the cluster Mn 8 Fe 4 O 12 (O 2 CC 6 H 4 CHCH 2 ) 16 (H 2 O) 4 , cross-linked with polystyrene (the nanocarrier), under miniemulsion conditions is described. By including a branched hydrophobe, iso-octane, the resulting nanobeads are porous and ∼70 nm in diameter. The increased surface area of the nanobeads compared to nonporous nanobeads leads to an enhancement in relaxivity; r 1 increases from 3.8 to 5.2 ± 0.1 mM −1 s −1 , and r 2 increases from 11.9 to 50.1 ± 4.8 mM −1 s −1 , at 9.4 teslas, strengthening the potential for T 1 and T 2 imaging. Several metrics were used to assess stability, and the porosity produced no reduction in metal stability. Synchrotron X-ray fluorescence microscopy was used to demonstrate that the nanobeads remain intact in vivo. In depth, physicochemical characteristics were determined, including extensive pharmacokinetics, in vivo imaging, and systemic biodistribution analysis.

A reflection on ‘Protein coronas suppress the hemolytic activity of hydrophilic and hydrophobic nanoparticles’

“…As an example, inorganic and polymeric nanoparticles that showed a minimal hemolytic response in the presence of erythrocytes were developed. 1,13,14 Other researchers have likewise demonstrated a significant decrease in the toxicity of polystyrene nanoparticles by forming a protein corona. 15 Additionally, studies found that forming a protein corona around nanoparticles increases the colloidal stability of metal nanoparticles.…”

Molecular Parameters Promoting High Relaxivity in Cluster–Nanocarrier Magnetic Resonance Imaging Contrast Agents

“…We were surprised to discover that rather than enhancing the T 2 contrast, the relaxivity r 1 increased to 3.37 mM –1 s –1 and there was a decrease in r 2 to 11.07 mM –1 s –1 . This effect was amplified by increasing the porosity of the polymer nanocarrier, where the greater surface area led to an increase in relaxivity to an r 1 of 5.2 ± 0.1 mM –1 s –1 and r 2 increasing to 50.1 ± 4.8 mM –1 s –1 , with capabilities for T 1 and T 2 dual contrast . The Mn 8 Fe 4 -coPS nanobeads (see Figure ) have exhibited low cytotoxicity, increased blood circulation time, limited biodistribution, in vivo MR imaging, and in vivo integrity, based on synchrotron X-ray fluorescence microscopy .…”

“…24 This effect was amplified by increasing the porosity of the polymer nanocarrier, where the greater surface area led to an increase in relaxivity to an r 1 of 5.2 ± 0.1 mM −1 s −1 and r 2 increasing to 50.1 ± 4.8 mM −1 s −1 , with capabilities for T 1 and T 2 dual contrast. 25 The Mn 8 Fe 4 -coPS nanobeads (see Figure 3) have exhibited low cytotoxicity, increased blood circulation time, limited biodistribution, in vivo MR imaging, and in vivo integrity, based on synchrotron X-ray fluorescence microscopy. 25 Where the outer-sphere mechanism is a diffusion-dependent process, 26 these results suggest that surface-bound clusters contribute to the relaxivity in an inner-sphere-type mechanism involving direct and indirect interactions of water with the metal of the cluster.…”

“…25 The Mn 8 Fe 4 -coPS nanobeads (see Figure 3) have exhibited low cytotoxicity, increased blood circulation time, limited biodistribution, in vivo MR imaging, and in vivo integrity, based on synchrotron X-ray fluorescence microscopy. 25 Where the outer-sphere mechanism is a diffusion-dependent process, 26 these results suggest that surface-bound clusters contribute to the relaxivity in an inner-sphere-type mechanism involving direct and indirect interactions of water with the metal of the cluster.…”

A reliable workflow for improving nanoscale X-ray fluorescence tomographic analysis on nanoparticle-treated HeLa cells

“…Bio-nanotechnology, particularly with the usage of nanoparticles, has led to promising results in cancer diagnosis and treatment. 1 For example, paramagnetic Mn 8 Fe 4 - co -polystyrene nanobeads have the potential to be used as the exogenous contrast agent for T1–T2 magnetic resonance imaging, 2 and Fe 3 O 4 /TiO 2 nanocomposites could be introduced to enhance radiation effects in neuroblastoma treatment. 3 Despite the great potential of bio-nanotechnology, gaining insights into the interactions between nanomaterials and subcellular structures is crucial prior to their wide applications in vivo .…”