Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an external oscillating magnetic field. As a technique, it produces highly sensitive radiation-free tomographic images with absolute quantitation. Coupled with a high contrast, as well as zero signal attenuation at-depth, there are essentially no limitations to where can be imaged within the body. These characteristics enable various biomedical applications of clinical interest. In the opening sections of this review, the principles of image generation are introduced, along with a detailed comparison of the fundamental properties of this technique with other common imaging modalities. The main feature is a presentation on the up-to-date literature for the development of SPIONs tailored for improved imaging performance, and developments in the current and promising biomedical applications of this emerging technique, with a specific focus on theranostics, cell tracking and perfusion imaging. Finally, we will discuss recent progress in the clinical translation of MPI. As signal detection in MPI is almost entirely dependent on the properties of the SPION employed, this work emphasises the importance of tailoring the synthetic process to produce SPIONs demonstrating specific properties and how this impacts imaging in particular applications and MPI’s overall performance

Nanoparticles-based magnetic and photo induced hyperthermia for cancer treatment

Nanoscience provides several modalities to combat cancer disease effectively. Magnetic hyperthermia and photothermal therapy techniques are central research themes among various groups in the world by utilizing magnetic and optical characteristics of distinct or composite nanoentities. This review provides the current research on both the techniques and their successes towards clinical translation. This review discusses about the various heating mechanisms involved in magnetic and photo-induced hyperthermia. We have evaluated potential functional nanoparticles with excellent properties capable of providing innovative future solutions to current problems associated with these therapies. Several factors (extracellular and intracellular) have been covered and explained which may affect such thermal treatments. We have provided some instrumental and technical details of both the techniques that are important for consideration in using these modalities of treatments. A direct comparison of these two techniques and a further need of the combined therapy (magnetic hyperthermia plus photothermal therapy) was highlighted as a new pathway for cancer treatments

DMSA-coated cubic iron oxide nanoparticles as potential therapeutic agents

AIM: Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for cancer treatment. METHODS: Monodisperse cubic IONPs with a high value of saturation magnetization were synthesized by thermal decomposition method and functionalized with DMSA via ligand exchange reaction, and their cytotoxic effects on HeLa cells were investigated. RESULTS: DMSA functionalized cubic IONPs with an edge length of 24.5 ± 1.9 nm had a specific absorption rate value of 197.4 W/gFe (15.95 kA/m and 488 kHz) and showed slight cytotoxicity on HeLa cells when incubated with 3.3 × 10^{10}, 6.6 × 10^{10} and 9.9 × 10^{10} NP/mL for 24, 48 and 72 h. CONCLUSION: To the best of our knowledge, this is the first study to investigate both the cytotoxic effects of DMSA-coated cubic IONPs on HeLa cells and hyperthermia performance of these nanoparticles

The Role of Anisotropy in Distinguishing Domination of Néel or Brownian Relaxation Contribution to Magnetic Inductive Heating: Orientations for Biomedical Applications

Magnetic inductive heating (MIH) has been a topic of great interest because of its potential applications, especially in biomedicine. In this paper, the parameters characteristic for magnetic inductive heating power including maximum specific loss power (SLPmax), optimal nanoparticle diameter (Dc) and its width (ΔDc) are considered as being dependent on magnetic nanoparticle anisotropy (K). The calculated results suggest 3 different Néel-domination (N), overlapped Néel/Brownian (NB), and Brownian-domination (B) regions. The transition from NB- to B-region changes abruptly around critical anisotropy Kc. For magnetic nanoparticles with low K (K Kc) are opposite. The decreases of the SLPmax when increasing polydispersity and viscosity are characterized by different rates of d(SLPmax)/dσ and d(SLPmax)/dη depending on each domination region. The critical anisotropy Kc varies with the frequency of an alternating magnetic field. A possibility to improve heating power via increasing anisotropy is analyzed and deduced for Fe3O4 magnetic nanoparticles. For MIH application, the monodispersity requirement for magnetic nanoparticles in the B-region is less stringent, while materials in the N- and/or NB-regions are much more favorable in high viscous media. Experimental results on viscosity dependence of SLP for CoFe2O4 and MnFe2O4 ferrofluids are in good agreement with the calculations. These results indicated that magnetic nanoparticles in the N- and/or NB-regions are in general better for application in elevated viscosity media

Development and Characterization of Curcumin-Silver Nanoparticles as a Promising Formulation to Test on Human Pterygium-Derived Keratinocytes

Pterygium is a progressive disease of the human eye arising from sub-conjunctival tissue and extending onto the cornea. Due to its invasive growth, pterygium can reach the pupil compromising visual function. Currently available medical treatments have limited success in suppressing efficiently the disease. Previous studies have demonstrated that curcumin, polyphenol isolated from the rhizome of Curcuma longa, induces apoptosis of human pterygium fibroblasts in a dose- and time-dependent manner showing promising activity in the treatment of this ophthalmic disease. However, this molecule is not very soluble in water in either neutral or acidic pH and is only slightly more soluble in alkaline conditions, while its dissolving in organic solvents drastically reduces its potential use for biomedical applications. A nanoformulation of curcumin stabilized silver nanoparticles (Cur-AgNPs) seems an effective strategy to increase the bioavailability of curcumin without inducing toxic effects. In fact, silver nitrates have been used safely for the treatment of many ophthalmic conditions and diseases for a long time and the concentration of AgNPs in this formulation is quite low. The synthesis of this new compound was achieved through a modified Bettini's method adapted to improve the quality of the product intended for human use. Indeed, the pH of the reaction was changed to 9, the temperature of the reaction was increased from 90 °C to 100 °C and after the synthesis the Cur-AgNPs were dispersed in Borax buffer using a dialysis step to improve the biocompatibility of the formulation. This new compound will be able to deliver both components (curcumin and silver) at the same time to the affected tissue, representing an alternative and a more sophisticated strategy for the treatment of human pterygium. Further in vitro and in vivo assays will be required to validate this formulation

Synthesis of magnetic cobalt ferrite nanoparticles with controlled morphology, monodispersity and composition: the influence of solvent, surfactant, reductant and synthetic conditions

In our present work, magnetic cobalt ferrite (CoFe2O4) nanoparticles have been successfully synthesised by thermal decomposition of Fe(III) and Co(II) acetylacetonate compounds in organic solvents in the presence of oleic acid (OA)/ oleylamine (OLA) as surfactants and 1,2-hexadecanediol (HDD) or octadecanol (OCD-ol) as an accelerating agent. As a result, CoFe2O4 nanoparticles of different shapes were tightly controlled in size (range of 4–30 nm) and monodispersity (standard deviation only at ca. 5%). Experimental parameters, such as reaction time, temperature, surfactant concentration, solvent, precursor ratio, and accelerating agent, in particular, the role of HDD, OCD-ol, and OA/OLA have been intensively investigated in detail to discover the best conditions for the synthesis of the above magnetic nanoparticles. The obtained nanoparticles have been successfully applied for producing oriented carbon nanotubes (CNTs), and they have potential to be used in biomedical applications

Quantitative two-dimensional strain mapping of small core-shell FePt@Fe3O4 nanoparticles

We report a facile one-pot chemical synthesis of colloidal FePt@Fe3O4 core–shell nanoparticles (NPs) with an average diameter of 8.7 ± 0.4 nm and determine their compositional morphology, microstructure, two-dimensional strain, and magnetic hysteresis. Using various state-of-the-art analytical transmission electron microscopy (TEM) characterization techniques—including high resolution TEM imaging, TEM tomography, scanning TEM-high angle annular dark field imaging, and scanning TEM-energy dispersive x-ray spectroscopy elemental mapping—we gain a comprehensive understanding of the chemical and physical properties of FePt@Fe3O4 NPs. Additional analysis using x-ray photoelectron spectroscopy, x-ray diffraction, and superconducting quantum interference device magnetometry distinguishes the oxide phase and determines the magnetic properties. The geometric phase analysis method is effective in revealing interfacial strain at the core–shell interface. This is of fundamental interest for strain engineering of nanoparticles for desirable applications

Stable Iron Oxide Nanoflowers with Exceptional Magnetic Heating Efficiency: Simple and Fast Polyol Synthesis

Magnetically induced hyperthermia has reached a milestone in medical nanoscience and in phase III clinical trials for cancer treatment. As it relies on the heat generated by magnetic nanoparticles (NPs) when exposed to an external alternating magnetic field, the heating ability of these NPs is of paramount importance, so is their synthesis. We present a simple and fast method to produce iron oxide nanostructures with excellent heating ability that are colloidally stable in water. A polyol process yielded biocompatible single core nanoparticles and nanoflowers. The effect of parameters such as the precursor concentration, polyol molecular weight as well as reaction time was studied, aiming to produce NPs with the highest possible heating rates. Polyacrylic acid facilitated the formation of excellent nanoheating agents iron oxide nanoflowers (IONFs) within 30 min. The progressive increase of the size of the NFs through applying a seeded growth approach resulted in outstanding enhancement of their heating efficiency with intrinsic loss parameter up to 8.49 nH m2 kgFe-1. The colloidal stability of the NFs was maintained when transferring to an aqueous solution via a simple ligand exchange protocol, replacing polyol ligands with biocompatible sodium tripolyphosphate to secure the IONPs long-term colloidal stabilization

High magnetisation, monodisperse and water-dispersible CoFe@Pt core/shell nanoparticles

High magnetisation and monodisperse CoFe alloy nanoparticles are desired for a wide range of biomedical applications. However, these CoFe nanoparticles are prone to oxidation, resulting in the deterioration of their magnetic properties. In the current work, CoFe alloy nanoparticles were prepared by thermal decomposition of cobalt and iron carbonyls in organic solvents at high temperatures. Using a seeded growth method, we successfully synthesised chemically stable CoFe@Pt core/shell nanostructures. The obtained core/shell nanoparticles have high saturation magnetisation up to 135 emu g−1. The magnetisation value of the core/shell nanoparticles remains 93 emu g−1 after being exposed to air for 12 weeks. Hydrophobic CoFe@Pt nanoparticles were rendered water-dispersible by encapsulating with poly(maleic anhydride-alt-1-octadecene) (PMAO). These nanoparticles were stable in water for at least 3 months and in a wide range of pH from 2 to 11

Estimation of progression of multi-state chronic disease using the Markov model and prevalence pool concept

<p>Abstract</p> <p>Background</p> <p>We propose a simple new method for estimating progression of a chronic disease with multi-state properties by unifying the prevalence pool concept with the Markov process model.</p> <p>Methods</p> <p>Estimation of progression rates in the multi-state model is performed using the E-M algorithm. This approach is applied to data on Type 2 diabetes screening.</p> <p>Results</p> <p>Good convergence of estimations is demonstrated. In contrast to previous Markov models, the major advantage of our proposed method is that integrating the prevalence pool equation (that the numbers entering the prevalence pool is equal to the number leaving it) into the likelihood function not only simplifies the likelihood function but makes estimation of parameters stable.</p> <p>Conclusion</p> <p>This approach may be useful in quantifying the progression of a variety of chronic diseases.</p