Pseudo-single domain colloidal superparamagnetic nanoparticles designed at a physiologically tolerable AC magnetic field for clinically safe hyperthermia.

Magnetic nanofluid hyperthermia (MNFH) with pure superparamagnetic nanoparticles (P-SPNPs) has drawn a huge attraction for cancer treatment modality. However, the low intrinsic loss power (ILP) and attributable degraded-biocompatibility resulting from the use of a heavy dose of P-SPNP agents as well as low heat induction efficiency in biologically safe AC magnetic field (HAC,safe) are challenging for clinical applications. Here, we report an innovatively designed pseudo-single domain-SPNP (PSD-SPNP), which has the same translational advantages as that of conventional P-SPNPs but generates significantly enhanced ILP at HAC,safe. According to the analyzed results, the optimized effective relaxation time, τeff, and magnetic out-of-phase susceptibility, χ'', precisely determined by the particle size at the specific frequency of HAC,safe are the main reasons for the significantly enhanced ILP. Additionally, in vivo MNFH studies with colloidal PSD-SPNPs strongly demonstrated that it can be a promising agent for clinically safe MNFH application with high efficacy.

Magneto-plasmonic nanostars for image-guided and NIR-triggered drug delivery.

Smart multifunctional nanoparticles with magnetic and plasmonic properties assembled on a single nanoplatform are promising for various biomedical applications. Owing to their expanding imaging and therapeutic capabilities in response to external stimuli, they have been explored for on-demand drug delivery, image-guided drug delivery, and simultaneous diagnostic and therapeutic (i.e. theranostic) applications. In this study, we engineered nanoparticles with unique morphology consisting of a superparamagnetic iron oxide core and star-shaped plasmonic shell with high-aspect-ratio gold branches. Strong magnetic and near-infrared (NIR)-responsive plasmonic properties of the engineered nanostars enabled multimodal quantitative imaging combining advantageous functions of magnetic resonance imaging (MRI), magnetic particle imaging (MPI), photoacoustic imaging (PAI), and image-guided drug delivery with a tunable drug release capacity. The model drug molecules bound to the core-shell nanostars were released upon NIR illumination due to the heat generation from the core-shell nanostars. Moreover, our simulation analysis showed that the specific design of the core-shell nanostars demonstrated a pronounced multipolar plasmon resonance, which has not been observed in previous reports. The multimodal imaging and NIR-triggered drug release capabilities of the proposed nanoplatform verify their potential for precise and controllable drug release with different applications in personalized medicine.

Dynamic magnetic characterization and magnetic particle imaging enhancement of magnetic-gold core-shell nanoparticles.

Multifunctional nanoparticles with a magnetic core and gold shell structures are emerging multi-modal imaging probes for disease diagnosis, image-guided therapy, and theranostic applications. Owing to their multi-functional magnetic and plasmonic properties, these nanoparticles can be used as contrast agents in multiple complementary imaging modalities. Magnetic particle imaging (MPI) is a new pre-clinical imaging system that enables real-time imaging with high sensitivity and spatial resolution by detecting the dynamic responses of nanoparticle tracers. In this study, we evaluated the dynamic magnetic properties and MPI imaging performances of core-shell nanoparticles with a magnetic core coated with a gold shell. A change in AC hysteresis loops was detected before and after the formation of the gold shell on magnetic core nanoparticles, suggesting the influence of the core-shell interfacial effect on their dynamic magnetic properties. This alteration in the dynamic responses resulted in an enhancement of the MPI imaging capacity of magnetic nanoparticles. The gold shell coating also enabled a simple and effective functionalization of the nanoparticles with a brain glioma targeting ligand. The enhanced MPI imaging capacity and effective functionality suggest the potential application of the magnetic-gold core-shell nanoparticles for MPI disease diagnostics.

Magnetic Relaxation of Intracellular Magnetic Nanoparticles for Hyperthermia.

Magnetic nanoparticles have been studied extensively for biomedical applications over the past decades. One of the promising applications of magnetic nanoparticles is hyperthermia, which refers to thermal treatment for cancer. To achieve adequate heat at target sites, it is essential to develop magnetic nanoparticles with high heating efficiency and to optimize external magnetic fields. Here, we discuss the heating mechanism of magnetic nanoparticles, the influence of the intracellular environment on magnetic behavior and heat generation, and recent advances in methods of heating efficiency assessment.

Giant Magnetic Heat Induction of Magnesium-Doped γ-Fe2 O3 Superparamagnetic Nanoparticles for Completely Killing Tumors.

Magnetic fluid hyperthermia has been recently considered as a Renaissance of cancer treatment modality due to its remarkably low side effects and high treatment efficacy compared to conventional chemotheraphy or radiotheraphy. However, insufficient AC induction heating power at a biological safe range of AC magnetic field (Happl ·fappl < 3.0-5.0 × 109 A m-1 s-1 ), and highly required biocompatibility of superparamagnetic nanoparticle (SPNP) hyperthermia agents are still remained as critical challenges for successful clinical hyperthermia applications. Here, newly developed highly biocompatible magnesium shallow doped γ-Fe2 O3 (Mg0.13 -γFe2 O3 ) SPNPs with exceptionally high intrinsic loss power (ILP) in a range of 14 nH m2 kg-1 , which is an ≈100 times higher than that of commercial Fe3 O4 (Feridex, ILP = 0.15 nH m2 kg-1 ) at Happl ·fappl = 1.23 × 109 A m-1 s-1 are reported. The significantly enhanced heat induction characteristics of Mg0.13 -γFe2 O3 are primarily due to the dramatically enhanced out-of-phase magnetic susceptibility and magnetically tailored AC/DC magnetic softness resulted from the systematically controlled Mg2+ cations distribution and concentrations in octahedral site Fe vacancies of γ-Fe2 O3 instead of well-known Fe3 O4 SPNPs. In vitro and in vivo magnetic hyperthermia studies using Mg0.13 -γFe2 O3 nanofluids are conducted to estimate bioavailability and biofeasibility. Mg0.13 -γFe2 O3 nanofluids show promising hyperthermia effects to completely kill the tumors.

Hyperthermia and chemotherapy using Fe(Salen) nanoparticles might impact glioblastoma treatment.

We previously reported that µ-oxo N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.

A possibility of hyperthermia treatment using MRI equipment.

A possibility of hyperthermia treatment using a magnetic resonance imaging (MRI) is discussed. A resonant circuit consisting of a closed connection of an inductor and a capacitor raised its temperature by an applied magnetic field. As the resonant circuit is heated efficiently, it can be used as an implant for the hyperthermia. It was indicated that a RF pulse of a commercial MRI system under normal diagnosis procedure could be used for the excitation source.