nanostructured metal complexes for targeted delivery in alzheimer’s therapy

Alzheimer’s disease (ad) is a progressive neurodegenerative disorder characterized by amyloid-β (aβ) aggregation, tau hyperphosphorylation, metal-ion dyshomeostasis, oxidative stress, and chronic neuroinflammation, all of which contribute to cognitive decline and neuronal loss. increasing evidence highlights the critical role of aberrant transition metals, such as copper, iron, zinc, and aluminum, in accelerating protein misfolding and redox imbalance, thereby amplifying disease pathology. conventional therapies have shown limited efficacy due to poor blood–brain barrier (bbb) penetration, lack of specificity, and inability to target multiple pathogenic pathways simultaneously. emerging nanostructured metal complexes offer a novel multimodal approach that combines tunable physicochemical properties, versatile ligand functionalization, and incorporation into advanced nanoformulations (e.g., liposomes, dendrimers, and polymeric nanoparticles). these systems enhance bbb permeability, enable targeted delivery, provide controlled drug release, and reduce systemic toxicity. mechanistically, they inhibit aβ aggregation, modulate tau hyperphosphorylation, chelate excess metal ions, and provide antioxidant and anti-inflammatory neuroprotective effects. copper-, iron-, zinc-, ruthenium-, and platinum-based complexes have demonstrated promising preclinical efficacy, particularly when integrated into ligand-decorated, stimuli-responsive, or multifunctional theranostic platforms. synergistic co-delivery with small molecules or genetic materials further expands the therapeutic versatility. the remaining challenges are bbb navigation, precision targeting, scalable manufacturing, and regulatory approval. leveraging precision medicine, artificial intelligence, and computational modeling can accelerate rational design, optimization, and clinical translation. overall, nanostructured metal complexes represent a cutting-edge, multitargeted, and clinically translatable strategy for ad therapy.