Hybrid Nanomaterials for Next-Generation CNS Theranostics & Targeted Delivery

Central nervous system (CNS) theranostics represents an evolving frontier in nanomedicine, seeking to unify diagnosis and therapy within a single, precisely engineered platform. Despite rapid progress, therapeutic access to the brain remains profoundly restricted by the blood–brain barrier (BBB), which tightly regulates molecular traffic, and by the presence of ATP-binding cassette efflux transporters that actively remove therapeutic agents, sustaining multidrug resistance and limiting drug efficacy. Hybrid nanomaterials, designed through the combination of metallic, polymeric, lipidic, and biomimetic components, have emerged as promising multifunctional systems capable of addressing the challenges of the CNS redox and metal-ion microenvironment, the imbalance of which contributes both to neurodegenerative disorders and to the vulnerabilities of brain tumours such as glioblastoma.

Iron-based systems illustrate this potential particularly well. Magnetic and catalytic iron-based nanostructures can traverse the BBB, catalyse ferroptosis-driven cancer cell death, and provide concurrent imaging functionalities through MRI and related modalities. However, achieving successful therapeutic outcomes through the inhibition of ferroptosis in neurodegenerative diseases such as Parkinson’s, Alzheimer’s, multiple sclerosis, or epilepsy remains equally challenging, highlighting the contrasting and context-dependent nature of iron-mediated oxidative processes within the CNS. Plus, more broadly, the need to understand how redox-active metals and reactive-oxygen pathways can be harnessed or restrained depending on disease context.

Nonetheless, the field remains fragmented across disciplines, and substantial barriers persist regarding reproducibility, scalable manufacturing, and the long-term fate and safety of these constructs in neural tissues.

This Research Topic aims to integrate materials engineering, iron biology, drug resistance, and biomedical imaging into a coherent framework for next-generation CNS theranostics. The primary goal is to identify and characterize nanoplatforms that achieve effective barrier penetration, modulation of multidrug resistance, and real-time image-guided therapy within reproducible, safe, and clinically translatable architectures. We welcome mechanistic and translational studies that deepen our understanding of iron-driven reactivity, ferroptosis control, and transport mechanisms across the BBB, as well as contributions establishing design principles, characterisation standards, and translational benchmarks for clinical advancement. This initiative also seeks to stimulate the emergence of new hypotheses and mechanistic insights into yet-unknown dimensions of drug resistance in neurological disorders.

To gather further insights in the realm of hybrid nanomaterials for CNS therapy and imaging, we welcome articles addressing, but not limited to, the following themes:

• Hybrid nanomaterial design and engineering - including core–shell, Janus, and framework architectures; surface functionalisation; protein-corona control; and scalable, GMP-compatible synthesis routes.
• Barrier crossing strategies - receptor- and adsorptive-mediated transcytosis, focused ultrasound-assisted BBB modulation, intranasal nose-to-brain delivery, and biomimetic cell-membrane camouflage, linking physicochemical structure to brain accumulation.
• Iron biology and resistance mechanisms - exploration or correction of ferroptosis processes; reversal of ATP-binding cassette transporter-mediated and adaptive multidrug resistance; and co-delivery of efflux inhibitors, genetic payloads, or modulatory agents.
• Imaging and translational frameworks - multimodal platforms enabling MRI, magnetic particle imaging, fluorescence, photoacoustic, or PET/SPECT visualisation, together with biodistribution, pharmacokinetic, biodegradation, and regulatory studies.
• Mechanistic and theoretical perspectives - unveiling new or poorly understood dimensions of resistance and ferroptosis regulation, fostering conceptual advances for future CNS theranostic strategies.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: CNS theranostics, Receptor-mediated transcytosis, Magneto-catalytic nanozymes, Ferroptosis, Multidrug resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.