Engineered nanoparticles for mitigating nervous system infections

Infections of the nervous system represent a heterogeneous and highly challenging disease category that includes both central nervous system (CNS) and peripheral nervous system (PNS) infections. These infections mainly include meningitis, encephalitis, cerebral malaria, toxoplasmosis, neurotuberculosis, viral-associated neurocognitive disorders, and PNS infections. Despite advances in antimicrobial therapies and supportive care, they remain among the leading causes of mortality and long-term disability worldwide. This review provides an in-depth overview of nanotechnology-assisted approaches to the treatment and diagnosis of CNS and PNS infections. We also discuss how diverse nanomaterials, including polymeric and lipid vesicles, as well as inorganic, biomimetic, catalytic, and stimuli-responsive materials, are engineered to overcome biological barriers, such as the blood-brain, blood-cerebrospinal fluid (CSF), and blood-nerve barriers, to target nervous system infections. Most importantly, nanomaterials are used not only to deliver therapeutics to target sites or improve diagnostics but also to interact with and manipulate biological processes to combat infections. The review also covers emerging trends in delivering nanomaterials to target nervous system infections, including intranasal delivery, biomimetic transcytosis, and pathogen-inspired mechanisms, as well as nano-assisted sensing approaches in CSF and peripheral biofluids. We further unify therapeutic and diagnostic approaches, highlighting nanotechnology's potential to address unmet medical needs.