Nanomedicine for neuroinflammation modulation: Next-generation nano-immunotherapies for neurodegenerative disorders

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, and multiple sclerosis, are increasingly recognized as consequences of persistent neuroimmune dysregulation rather than isolated neuronal loss. Chronic microglial and astrocytic activation, NF-κB/NLRP3 inflammasome signalling, cytokine amplification, oxidative stress, mitochondrial dysfunction, and blood–brain barrier (BBB) disruption converges to form a self-propagating inflammatory network that accelerates neurodegeneration. Despite expanding mechanistic insight, conventional anti-inflammatory therapies remain constrained by limited BBB penetration, poor cellular specificity, and single-target efficacy. Nanomedicine offers an emerging strategy by enabling targeted delivery and material-driven modulation of neuroinflammatory pathways. This review critically integrates advances in polymeric, lipid-based, metal, carbon, and biomimetic nanoplatforms, highlighting how engineered nano systems actively regulate neuroimmune signalling rather than functioning solely as passive carriers. Mechanistic emphasis is placed on nano-enabled control of NF-κB/NLRP3 activation, microglial polarization, cytokine cascades, redox imbalance, mitochondrial stabilization, and BBB transport. The novelty of this review lies in integrating neuroinflammatory circuitry with nanomaterial design parameters to establish a systems-level framework for multifunctional nano-immunotherapies capable of concurrently targeting inflammatory signalling, oxidative injury, and neurovascular dysfunction. Emerging biomimetic and immune cell–derived platforms are discussed as next-generation approaches for cell-selective engagement within inflamed neural microenvironments. Key translational challenges, including immune compatibility, biodegradability, long-term safety, and disease-stage–specific optimization, are also addressed. Precision nano-immunotherapy is positioned as a promising avenue toward interventions in neurodegenerative disorders.