Pseudo single domain NiZn-γFe2O3colloidal superparamagnetic nanoparticles for MRI-guided hyperthermia application.

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) is highly desirable in cancer treatment because it can allow for diagnosis, therapeutics, and prognosis simultaneously. However, the application of currently developed iron-oxide based superparamagnetic nanoparticles (IOSPNPs) for an MRI-guided MNFH agent is technically limited by the low AC heat induction power at the physiologically tolerable range of AC magnetic field (HAC,safe), and the low transverser2-relaxivity responsible for the insufficient heating of cancers, and the low resolution of contrast imaging, respectively. Here, pseudo single domain colloidal NixZn1-x-γFe2O3(x = 0.6) superparamagnetic nanoparticle (NiZn-γFe2O3PSD-SPNP) physically and theoretically designed at theHAC,safe, specifically by the applied frequency, is proposed for a highly enhanced MRI-guided MNFH agent application. The NiZn-γFe2O3PSD-SPNP showed the superparamagnetic characteristics, significantly enhanced AC heat induction performance (ILP = 6.3 nHm2kg-1), highly improved saturation magnetization (Ms= 97 emu g-1Fe, 3.55 × 105A m-1) andr2-relaxivity (r2 = 396 mM-1s-1) that are desirable for highly efficient MRI-guided MNFH agent applications. According to the analyzed results, the remarkably enhanced effective relaxation time constant and its dependent out-of-phase magnetic susceptibility, as well as the DC/AC magnetic softness optimized by the PSD-SPNP at theHAC,safewere revealed as the main physical reason for the significance. All the fundamentalin vitroandin vivoexperimental results demonstrated that the physically designed NiZn-γFe2O3PSD-SPNP is bio-technically feasible for a highly efficient MRI-guided MNFH agent for future cancer nanomedicine.

Reliable evaluation method of heating power of magnetic nanofluids to directly predict the tumor temperature during hyperthermia.

Reliable measurement of heating power of magnetic nanofluids (MNs) to accurately predict the AC heat-induction performance in tumors is highly desirable for clinical magnetic nanofluids hyperthermia (MNFH) application because it can save time for screening the performance of newly developed MNFH agent and minimize the over-use of animals dramatically. Here, a bio-mimicking phantom model, called Pseudo-Tumor Environment System (P-TES), biochemically designed by considering the external and internal critical factors related to the complex biological environments is proposed to provide a highly reliable evaluation method of heating performance of MNs for in-vivo MNFH applications. According to the experimentally analyzed results, the heating power of MNs measured using the P-TES is well accorded with the heating temperature measured in the tumors during in-vivo MNFH. This result strongly demonstrates that the proposed P-TES can be recommended as a standardized measurement method of heating performance of MNs for clinical MNFH application.

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.

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.

Magnetically softened iron oxide (MSIO) nanofluid and its application to thermally-induced heat shock proteins for ocular neuroprotection.

Magnetically softened iron oxide (MSIO) nanofluid, PEGylated (Mn0.5Zn0.5)Fe2O4, was successfully developed for local induction of heat shock proteins (HSPs) 72 in retinal ganglion cells (RGCs) for ocular neuroprotection. The MSIO nanofluid showed significantly enhanced alternating current (AC) magnetic heat induction characteristics including exceptionally high SLP (Specific Loss Power, > 2000 W/g). This phenomenon was resulted from the dramatically improved AC magnetic softness of MSIO caused by the magnetically tailored Mn(2+) and Zn(2+) distributions in Fe3O4. In addition, the MSIO nanofluid with ultra-thin surface coating layer thickness and high monodispersity allowed for a higher cellular uptake up to a 52.5% with RGCs and enhancing "relaxation power" for higher AC heating capability. The RGCs cultured with MSIO nanofluid successfully induced HSPs 72 by magnetic nanofluid hyperthermia (MNFH). Moreover, it was interestingly observed that systematic control of "AC magnetically-induced heating up rate" reaching to a constant heating temperature of HSPs 72 induction allowed to achieve maximized induction efficiency at the slowest AC heating up rate during MNFH. In addition to in-vitro experimental verification, the studies of MSIO infusion behavior using animal models and a newly designed magnetic coil system demonstrated that the MSIO has promising biotechnical feasibility for thermally-induced HSPs agents in future glaucoma clinics.

Physical contribution of Néel and Brown relaxation to interpreting intracellular hyperthermia characteristics using superparamagnetic nanofluids.

In this work, the AC magnetically-induced heating characteristics of various viscous nanofluids with either soft ferrite (Fe3O4) or hard ferrite (CoFe2O4) superparamagnetic nanoparticles (SPNPs) were investigated to empirically and physically interpret the contribution of "Néel relaxation loss power, P(Néel relaxation loss)," or "Brown relaxation loss power, P(Brown relaxation loss)," to the total AC heat generation of intracellular hyperthermia or in-vivo hyperthermia. It was found that the contribution of P(Brown relaxation loss) to the total AC heating power, P(totaI), and the specific loss power (SLP) was severely affected by the surrounding environment (or in-vivo environment) while the contribution of P(Néel relaxation loss) to the P(total) was independent of the variation of surrounding environment. Furthermore, all the theoretical and experimental results strongly suggested that highly efficacious intracellular hyperthermia (or in-vivo hyperthermia) modality can be achieved by enhancing the P(Néel relaxation loss) rather than the P(Brown relaxation loss) of SPNP agents in nanofluids.