Neuronal Membrane-Coated Mesoporous Ceria Nanoparticles for Blood–Brain Barrier Crossing and Mitigation of Neurodegeneration

Even after several attempts, very few therapeutics have been successfully translated clinically for mitigating neurodegeneration. The major obstacle to effective treatment is the highly restrictive blood–brain barrier, which impedes the free access of antigens and therapeutics to the brain parenchyma, thereby limiting their therapeutic efficacy. Addressing this challenge, we have devised a biologically inspired nanoformulation using a neural cell membrane and ceria nanoparticles (NM@MCN-MM) for antioxidant activity and neuroprotection. The mesoporous ceria nanoparticle was optimized and fabricated using a soft template method and subsequently encapsulated within Neuro-2a (N2a) cell membranes. Given that mitochondrial dysfunction, increased oxidative stress, and calcium imbalance are common hallmarks of various neurodegenerative diseases, NM@MCN-MM has demonstrated promising results in addressing these pathological characteristics. Additionally, the formulation exhibits enhanced systemic circulation with natural brain-homing properties and reduced immunogenicity, which collectively improve the brain-targeting efficiency of the developed carrier and facilitate BBB permeation, as estimated through LC-MS/MS and optical live imaging using indocyanine green as a fluorescent probe. The significant findings of the developed biomimetic formulation against common hallmarks of neurodegenerative diseases, retaining the biomimetic catalytic activity of nanoceria upon an increase in size, suggest its potential in wider applications for mitigating other neurodegenerative diseases.