Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement

Abstract

composition [14,19] of MNPs. For example, we obtained an SLP of 3417 W metal g 1 − at a field of 33 kA m −1 and 380 kHz in Co 0.03 Mn 0.27 Fe 2.7 O 4 /SiO 2 MNPs. [14] In recent years, great progress has been made on in vivo magnetic hyperthermia treatments of solid tumors. [20][21][22][23][24][25][26][27] It was reported that tumors in mice can be eliminated after receiving magnetic hyperthermia treatment using coreshell MNPs. [6] Systemically delivered ZnMn-ferrite MNPs were shown to have increased the intratumoral temperature to above 42 °C in mice, which significantly inhibited prostate cancer growth. [28] More recently, studies also focused on heat-triggered drug release and highly efficient heat-induced immunotherapy instead of using heating alone. [20,24,29] In addition to injected or delivered MNPs, magnetic composite implants and magnetic scaffolds were also used for local hyperthermia. [30][31][32][33][34][35][36][37] The first magnetic hyperthermia was attempted in 1957 for metastasis in lymph nodes. [1] In 2005, the first clinical application of interstitial hyperthermia using MNPs in locally recurrent prostate cancer was reported. [38] Maier-Hauff et al. published results from a Phase I clinical study involving 14 patients with recurrent glioblastoma multiforme. [39,40] These clinical studies were performed using a commercial machine (Mag-Force MFH 300F). A roadmap for magnetic hyperthermia Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn 0.3 Fe 2.7 O 4 nanoparticles with low concentration, is reported. Under an AC field of 4 kA m −1 at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W g g 1 1 m me et ta al l − − and an intrinsic loss power of 47 nHm 2 kg −1 , which is enhanced by 50-fold compared to randomly oriented samples. The highperformance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.

Heat Generation in Magnetic Hyperthermia by Manganese Ferrite-Based Nanoparticles Arises from Néel Collective Magnetic Relaxation

“…This could be obtained by tuning the cation distribution in the spinel structure of magnetite/maghemite NPs or by doping NPs with Mn or Zn to decrease its anisotropy. Indeed, Mn-ferrite and Zn-doped iron oxide nanomaterials have shown interesting in vivo performance under clinical conditions, while MnZn-ferrite NPs also show promising applications. ,, …”

Simultaneous Enhancement of Magnetothermal and Photothermal Responses by Zn, Co Co‐Doped Ferrite Nanoparticles

“…The main difference between such an environment and an aqueous solution is that the motion of NPs is prohibited, leading to much lower heating capabilities than that Small 2022, 18, 2205037 in a solution where NPs are free to move and align in the AC field. [23] In our ex vivo experiments, 50 µL NP aqueous solution with a concentration of 2.7 mg mL −1 was injected into the dorsal muscle of mice (dosage of 6.75 mg kg −1 , comparable to that used for MRI and much lower than typically used for hyperthermia). While the effective NP concentration in the body is difficult to quantify, it is expected to be much smaller than the original concentration of the solution as the NPs diffuse rapidly after subcutaneous injection.…”

“…[4,[20][21][22] Our previous work suggests that Zn-doped ferrites (Zn 0.3 Fe 2.7 O 4 ) exhibited higher specific loss power (SLP) than Fe 3 O 4 owing to their higher magnetization. [20,23,24] Co addition, on the other hand, can increase the magnetic anisotropy, which can enhance the SLP at higher fields. [20] Recent trends exploring the potential of combining MHT and PTT to produce cumulative local heating can bring about high heating efficiency in hyperthermia therapy.…”

Enhanced Magnetic Hyperthermia Performance of Zinc Ferrite Nanoparticles under a Parallel and a Transverse Bias DC Magnetic Field

“…This effect is probably due to the differences in the orientations of the total field in the two cases, as explained for the immobilized samples. This observation might have practical applications as both in vivo and in vitro, the recent experimental data have shown that the pre-alignment of MNPs during the cellular uptake [ 25 ] or in a bone cement, [ 64 ] significantly enhances the MH efficiency when the AMF was applied along the direction of the alignment. Our results suggest that the superposition of a perpendicular static DC field during MH might significantly increase the heat released, as compared to the parallel configuration.…”