Advances in magnetic nanoparticles for molecular medicine

Abstract

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular levels. These unique capabilities have opened new avenues in emerging fields such as genome editing, cell therapies, and neuroscience, underpinned by a growing understanding of nanomagnetism and the molecular mechanisms responding to mechanical and thermal cues. Research on MNPs as a versatile synthetic material capable of engineering control at the cellular and molecular levels holds great promise for advancing the frontiers of molecular medicine, including areas such as genome editing and synthetic biology. This review summarizes recent clinical studies showcasing the classical applications of MNPs and explores their integration into molecular medicine, with the goal of inspiring the development of next-generation MNP-based platforms for disease treatment.

Fig. 1. Synthesis of iron oxide nanoparticles. (A) Ferumoxytol synthesized via co-precipitation. (Reproduced with permission from ref. , ©2023 John Wiley and Sons). B through L are iron oxide nanoparticles synthesized via thermodecomposition. (B) Magnetite nanocubes. (Reproduced with permission from ref. , ©2009 American Chemical Society). (C) Magnetite nanostars. (Reproduced with permission from ref. , ©2011 American Chemical Society). (D) Magnetite nanorods. (Reproduced with permission from ref. , ©2012 American Chemical Society). (E)–(H). Magnetite nanoparticles from 6 to 40 nm. (Reproduced with permission from ref. , ©2011 American Chemical Society). (I)–(L). Wüstite nanoparticles from 14 to 100 nm. (Reproduced with permission from ref. , ©2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim).

Fig. 2. Applications of magnetic nanoparticles. Applications of MNPs can be broadly categorized into four groups based on the physical or chemical properties emphasized.

Fig. 3. Spatial control of in vivo gene editing. Baculoviral vectors (BV) labeled with MNPs facilitate localized gene editing through the combined effects of magnetic activation and complement inhibition. (A) TEM images of MNPs, BV, and MNP-BV hybrids. (B) Schematic illustration of MNP-BV-mediated transgene delivery to the mouse liver. (C) Bioluminescence analysis of transgene expression: mice injected with MNP-BV-LUC and exposed to a magnetic field exhibited strong luminescence in the liver. In contrast, no luminescence was observed in mice treated with BV-LUC alone or with MNP-BV-LUC without magnetic field application. C3 knockout mice served as controls. (D) Assessment of gene editing in vital organs. (Reproduced with permission from ref. , ©2018 Springer Nature).

Fig. 4. Magnetic force-induced neuron activation. (A) Design of the nanoscale magnetic torquer system. The m-Torquer system acts as a nanoscale magnetic compass to generate the Fτ needed for magnetomechanical signal transduction. (B) Schematic of genetic encoding of Piezo1 and its magnetomechanical gating with specifically targeted m-Torquer with Myc antibody. (C) Temporal repetitive stimulation of Piezo1 with m-Torquer-treated (red) neurons. WGA-m-Torquer-treated (blue) neurons were used as controls. (Reproduced with permission from ref. , ©2021 Springer Nature).

Fig. 5. Size-dependent heating of MNPs. SAR was measured for MNPs ranging from 6 to 40 nm dispersed in DI water, using an AMF at 325 kHz and 20.7 kA m⁻¹. The solid curve represents the theoretical SAR predictions according to the LRT model. (Reproduced with permission from ref. , ©2017 American Chemical Society).

Fig. 6. Schematic illustrating tissue vitrification, convective warming, and nanowarming. (A) Tissues are harvested from a donor. (B) Tissues are loaded in a vial with CPA (VS55) and MNPs in a stepwise protocol, vitrified by standard convection, and stored at cryogenic temperatures. Warming by standard convection (C) leads to failure in larger 50-ml systems (D). Nanowarming in an alternating magnetic field, an inductive RF coil that stimulates nanoparticle heating (E), avoids warming failure and renders the tissue suitable for further testing or use (F). (Reproduced with permission from ref. , ©2017 The American Association for the Advancement of Science).

Fig. 7. Remote neural activation in vivo using radio waves. (A) Schematic of activation system. Ferritin-TRPV1 complexes were delivered to hypothalamic glucose-sensing neurons via viral transfection. (B) Treatment with a radio frequency AMF (465 kHz) elevated blood glucose levels in mice. (Reproduced with permission from ref. , ©2016 Springer Nature).

Fig. 8. MNP-mediated heterogeneous Fenton reaction. (A) Schematic of enhancing surface Fenton reaction via intraparticle electron transport. In a composite nanoparticle of magnetite (Fe₃O₄) shell and a core of low-valence iron (Fe⁰ & Fe²⁺), the low-valence iron can accelerate the catalysis by reducing the octahedral Fe³⁺ in the magnetite shell to Fe²⁺ through intraparticle electron transport. (B) Catalytic activities of MNPs of various compositions. (Reproduced with permission from ref. , ©2023 John Wiley and Sons).

Xiaoyue Yang

Sarah E. Kubican

Zhongchao Yi

Sheng Tong