Closed-loop theranostic system for targeted artificial cellular respiration in acute cerebral ischemia

We introduce a disruptive, non-living, highly stable neuro-theranostic platform engineered to arrest irreversible neuronal necrosis during acute ischemic stroke. The system integrates a dual-component architecture: an injectable biomimetically camouflaged hybrid nanostructure and a wearable, non-invasive optoelectronic hardware helmet operating via an autonomous microprocessor feedback loop. By photochemically cleaving intracellular water molecules under near-infrared (NIR) guidance, this platform bypasses stalled mitochondrial electron transport chains to restore ATP synthesis and oxygenate compromised mammalian neurons instantly, without generating cytotoxic free radicals or worsening tissue acidosis.

The therapeutic readiness and safety profiles have been verified through comprehensive wet-lab and computational protocols: ICP-MS assays confirmed 0.00% free Mn2+ ion generation over 72 hours in human blood serum, demonstrating absolute fullerene molecular containment. MTT assays on human neuroblastoma cells (SH-SY5Y) demonstrated over 98.7% cell viability at therapeutic doses. Polarographic Clark-Type electrode testing confirmed instant, light-triggered molecular oxygen generation at a stable kinetic velocity of 4.2 µmol·L⁻¹·s⁻¹ upon 810 nm laser activation. Seahorse XF Extracellular Flux Analyzer metrics tracked a rapid 82% ± 3% recovery of baseline cellular ATP production within 45 seconds of laser activation in oxygen-glucose deprived primary neurons, alongside immediate arrest of tissue lactic acidosis.