Authors: Qiyue Wang | Yuehao Gan | Fangyuan Li | Daishun Ling
Source: Accounts of Chemical Research (article, 2025-11-04)
Field: Materials Science — Biomaterials

Assembly-Driven Chemistry of Magnetic Nanoparticles: From Structural Design to Biomedical Applications ConspectusTailored magnetic nanoparticles (MNPs) have emerged as powerful tools in biomedical imaging, offering enhanced sensitivity, specificity, spatial resolution, and multifunctionality. Their unique physicochemical properties also open promising avenues for therapeutic applications. Continued innovation in MNP design is critical to fully exploit advanced imaging platforms─including high-field magnetic resonance imaging (MRI), magnetic particle imaging (MPI), and multimodal imaging systems─for early diagnosis and precision therapy. However, conventional strategies centered on tuning particle size, shape, composition, and crystallinity offer only limited control over intrinsic microscopic parameters such as magnetic moment orientation, defect structure, and electronic activity, which fundamentally govern imaging performance. This limitation has created a persistent bottleneck in the development of high-performance MNPs. Assembly driven chemical design offers a multiscale design paradigm that spans atomic, interfacial, and nanoscale levels. By inducing emergent collective behaviors not present in individual building blocks, this strategy significantly broadens the design space for optimizing MNP functionality.In this Account, we summarize our recent advances in the assembly driven chemical design of MNPs and their biomedical applications. At the atomic scale, controlled atomic rearrangements, defect engineering, and surface atom segregation are harnessed to fine-tune magnetic moment alignment, magnetic susceptibility, water exchange kinetics, and catalytic activity. At the interfacial level, the assembly of core-shell and organic-inorganic hybrid structures modulates exchange coupling interactions, enabling integrated diagnostic and therapeutic capabilities. At the nanoscale, ligand-mediated MNP assembly imparts stimuli responsiveness and facilitates the integration of multimodal imaging functions. These multiscale design strategies collectively establish robust structure-activity relationships and allow precise tailoring of MNPs for specific biomedical imaging modalities and therapeutic outcomes.We then highlight key breakthroughs enabled by these MNP assemblies. In advanced magnetic imaging, they overcome longstanding limitations in sensitivity and resolution, achieving an ultralow transverse-to-longitudinal relaxivity ratio and enhanced <i>T</i><sub>1</sub>-weighted contrast under high-field MRI, as well as submillimeter spatial resolution in MPI. These performance gains extend the imaging frontier to previously undetectable targets, such as isolated tumor cells as small as ∼0.16 mm, and enable real-time molecular imaging of neuronal signaling in vivo, paving the way for early diagnosis and imaging-guided therapy of malignancies and neurological diseases. Beyond imaging, atomic-scale reconfiguration enables MNPs to structurally mimic the active site architecture of metabolic enzymes such as xanthine oxidoreductase, thereby enabling tumor-selective metabolic therapy.Together, these findings underscore the transformative potential of assembly driven MNP design in next-generation biomedical imaging and precision medicine. We conclude by outlining future directions for constructing life-inspired, multiscale "transformative magnetic artificial molecules," to enable precise sensing and regulation of complex biological activities. Ultimately, assembly driven chemistry offers a robust and versatile framework for the rational development of high-performance MNPs, accelerating their clinical translation and inspiring new therapeutic innovations. Magnetic nanoparticles ; Magnetic particle imaging ; Nanoparticle ; Bottleneck ; Design elements and principles ; Magnetic resonance imaging ; Exploit Nanoparticle-Based Drug Delivery ; Characterization and Applications of Magnetic Nanoparticles ; Nanoplatforms for cancer theranostics