ZIF‐8‐Based Nanodelivery of Tectorigenin for Alleviating Skeletal Muscle Atrophy via Inhibition of Oxidative Stress and Inflammation
Year: 2026
Type: article
Abstract: BACKGROUND: Skeletal muscle atrophy is a pathological condition characterized by a progressive loss of muscle mass and function. Its core mechanisms involve an imbalance between protein synthesis and degradation, caused by oxidative stress and inflammation. Tectorigenin (TG) shows therapeutic potential but suffers from poor solubility and bioavailability. This study developed a zeolitic imidazolate framework-8 (ZIF-8) nanocarrier for TG (ZIF-8@TG) to enhance delivery efficacy against neurogenic muscle atrophy. METHODS: ZIF-8@TG nanoparticles were synthesized and characterized for size, drug loading, release profile and cytotoxicity. Their therapeutic effects were investigated in vitro using a nutrient deprivation-induced C2C12 myotube atrophy model and in vivo using a sciatic nerve crush injury-induced mouse model of muscle atrophy. Immunofluorescence staining and western blotting were performed to assess the effects of ZIF-8@TG on atrophic myotubes. Behavioural tests, immunofluorescence staining and western blotting were used to evaluate its impact on muscle atrophy in vivo. The underlying mechanisms were further explored through western blotting, electron microscopy, immunofluorescence staining and H&E staining. RESULTS: ZIF-8@TG nanoparticles (approx. 50 nm) exhibited pH-responsive release and efficient cellular uptake. In vitro, nutrient deprivation reduced myotube diameter by 53% (p < 0.01), whereas ZIF-8@TG treatment restored it to 92% of control levels, showing significantly better efficacy than free TG. In vivo, sciatic nerve injury decreased tibialis anterior muscle mass by 35% (p < 0.001) and mean myofiber cross-sectional area (CSA) by 41% (p < 0.001). ZIF-8@TG treatment significantly increased muscle mass to 74% and CSA to 93% of control values, whereas free TG resulted in non-significant improvements. Additionally, ZIF-8@TG improved motor function in mice following sciatic nerve crush. Mechanistically, the alleviation of skeletal muscle atrophy by ZIF-8@TG may be associated with regulation of excessive activation of the ubiquitin-proteasome system and autophagy-associated changes, along with enhanced protein synthesis-related Akt/mTOR signalling pathway during sciatic nerve crush-induced muscle atrophy, as well as an association with reduced oxidative stress and inflammation. CONCLUSIONS: ZIF-8@TG effectively delivers TG, alleviating muscle atrophy in vitro and in vivo. ZIF-8@TG treatment is associated with reduced oxidative stress and inflammation, preserved protein homeostasis and improved functional recovery, offering a promising nanotechnology-based therapy strategy for neurogenic skeletal muscle atrophy.
DOI: 10.1002/jcsm.70418
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,400
OpenAlex ID: W7225752680