Fe 3 ⁺-Activated fluorescence sensing and SEPHS1-mediated redox regulation via a PLGA nanoplatform for intracerebral hemorrhage
TL;DR
A multifunctional nanoplatform capable of simultaneous Fe 3 ⁺ detection and redox regulation is established, providing a promising strategy for mitigating ICH-induced brain injury.
Abstract
Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by high mortality and disability, largely driven by secondary brain injury associated with oxidative stress, iron overload, and neuronal senescence. However, effective therapeutic strategies remain limited. Here, we report the design of a microorganism-modified poly(lactic-co-glycolic acid) nanocarrier system ( 1-PLGA@SEPHS1 ) for the delivery of selenium phosphate synthase 1 (SEPHS1), a regulator of cellular redox homeostasis. Material characterization confirmed that 1-PLGA@SEPHS1 possesses a stable amorphous framework, high biocompatibility, and mesoporous features conducive to drug loading and controlled release. Functional assays demonstrated that SEPHS1 expression is progressively downregulated in the ICH model, and its deficiency exacerbates oxidative stress and neuronal senescence. In contrast, restoration of SEPHS1 via the nanocarrier reestablishes neuronal redox balance and improves neuronal survival. Importantly, 1-PLGA@SEPHS1 also functions as a fluorescent probe for Fe 3 ⁺, exhibiting rapid response kinetics, high selectivity, and excellent reversibility, enabling sensitive monitoring of iron overload in the ICH microenvironment. Animal experiments further verified that antioxidant intervention alleviates neurological deficits, supporting the protective role of SEPHS1 in neuronal injury. This study establishes a multifunctional nanoplatform capable of simultaneous Fe 3 ⁺ detection and redox regulation, providing a promising strategy for mitigating ICH-induced brain injury.