GLUT1‐Targeted Biomimetic Parishin‐Modified Nanoselenium for Organ Protection by Reestablishing Mitochondrial Homeostasis via Anti‐inflammatory and Antioxidant Pathways

Abstract

GLUT1‐targeted therapy is a promising approach for treating various diseases. However, overcoming the poor competitiveness of glucose‐analog ligands to bind glucose molecules is highly challenging. In this study, parishins isolated from Gastrodia elata are reported as high‐affinity GLUT1 ligands(‐9.859 kcal/mol for parishin A), identifying them as novel class of high‐potential GLUT1 ligands. Using G. elata extract, parishin‐modified selenium nanoparticles (P@Se NPs) in a green one‐pot process were prepared. P@Se NPs perform uniform size and well‐defined core‐shell structure, where the Se NP core was coated with G. elata extract (hydrodynamic diameter: 92.73±0.40 nm; zeta potential: −24.30±0.55 mV). In a liver injury model, P@Se NPs shows enhanced GLUT1‐mediated uptake (4.03‐fold higher than that in free dye) and liver targeting (1.34‐fold higher than that in free dye). P@Se NPs effectively alleviated hepatocyte necrosis induced by mitochondrial dysfunction and significantly improved key liver function indicators (AST, ALT, LDH, and T‐Bil). Mechanistically, P@Se NPs restore mitochondrial function by normalizing oxidative stress (MDA, CAT, and SOD) and anti‐inflammation (iNOS, IL‐1β, and TNF‐α), demonstrating effective GLUT1‐targeting‐assisted synergistic antioxidant and anti‐inflammatory effects for hepatoprotection. This study provides a novel biomimetic GLUT1‐targeted nanoplatform and offers a modern approach to developing traditional medicine components.