Magnetic Nanotransducers as a Universal Platform for Remote Cell Control: Mechanisms, Design, and Therapeutic...

Magnetogenetics represents a new paradigm in biomedicine that employs magnetic nanoparticles (MNPs) as nanotransducers for remote, contactless control of cellular functions in vivo with high spatiotemporal resolution. This review systematically examines three fundamental physical principles underlying magnetogenetics: the magnetomechanical principle, which enables generation of piconewton-scale forces to activate mechanosensitive Piezo1/2 and TRPV4 channels; local "hot-spot" heating, which allows mild activation of thermosensitive TRPV1, TRPA1, and TRPM8 channels without macroscopic tissue temperature elevation; and the principle of magnetically triggered biochemical modulation, encompassing both the controlled release of signaling molecules and the generation of reactive oxygen species (ROS) for remote activation of intracellular cascades. The critical role of nanoparticle physicochemical design-including control over size, shape, doping, and surface functionalization-in achieving target specificity and efficacy is discussed. We review current advances in the application of these approaches to remotely actuated stimulation of cardiomyocytes, cell-specific modulation of neuronal circuits, metabolic regulation, and targeted anticancer therapy, including induction of ferroptosis and modulation of the tumor immune microenvironment. Particular emphasis is placed on key challenges for clinical translation, namely, ensuring specificity of MNP delivery, long-term biosafety of genetic constructs and nanoparticles, standardization of stimulation protocols, and addressing issues of magnetic field penetration depth and focusing precision. By integrating advances in nanotechnology, genetic engineering, and cell biology, magnetogenetics opens new avenues for personalized therapy of neurodegenerative, cardiovascular, and oncological diseases. However, the approach has been subject to significant physical and biological criticism, including fundamental questions regarding the thermodynamic feasibility of nanoscale heating and the mechanical sufficiency of single-particle forces-critiques that temporarily marginalized the field. This review critically examines these controversies and argues that while second-generation systems (e.g., high-moment synthetic nanoparticles and magnetoelectric nanodiscs) have partially alleviated these concerns, rigorous validation and reproducibility remain paramount. Nonetheless, magnetogenetics represents a promising remote alternative to existing methods of cellular modulation.