OGP-loaded tannic acid-stabilized gold nanoparticles mitigates bone and muscle degeneration in osteosarcopenia

doi:10.1016/j.metadv.2026.02.004

Abstract

Abstract:

Osteosarcopenia, an age-related syndrome involving both bone and muscle loss, severely impairs mobility and quality of life. In this study, we constructed novel multifunctional nanomaterials, tannic acid-stabilized gold nanoparticles loaded with osteogenic growth peptide (Au@TA-OGP). The system integrates the polyphenol chemistry of tannic acid with peptide bioactivity to enable colloidally stable, biocompatible, and osteoinductive nanoparticles. Au@TA-OGP exhibited excellent cytocompatibility with macrophages and endothelial cells, while significantly enhancing osteogenic differentiation of osteoblastic cells. In an established osteosarcopenia mouse model, treatment with Au@TA-OGP restored bone microarchitecture, reduced osteoclast activity, and reduced muscle loss. Micro-CT and histological analyses revealed improved trabecular structure and reduced bone resorption and muscle histology showed enlarged myofibers with diminished fibrosis. No systemic toxicity was detected by serum biochemistry or major-organ histology. Together, these findings suggest that Au@TA-OGP provides a safe, multifunctional nanotherapy that promotes bone formation, inhibits resorption, and supports neuromuscular repair, offering translational potential for metabolic bone diseases with neuromuscular comorbidity.

Key words: Gold nanoparticles, Green synthesis, Biocompatibility, Osteosarcopenia, Osteogenic growth peptide, Ovariectomy, Sciatic nerve injury

Jiaming Wei, Jiarui Xue, Ke Zhao, Xunlu Yin, Kai Sun, Penghui Li, Chong Liu, Haojie Wang, Jiawen Zhan, Kexin Yang. OGP-loaded tannic acid-stabilized gold nanoparticles mitigates bone and muscle degeneration in osteosarcopenia[J]. Metals Advances, 2026, 41: 109-121.

Figures/Tables 7

Fig. 1. Green synthesis and effects of Au@TA-OGP—TA microwave-reduces and coats AuNPs (Au@TA), OGP is assembled on the surface to form Au@TA-OGP, which in vivo restores trabecular bone and improves muscle condition.

Fig. 2. Physicochemical characterization of Au@TA-OGP. (a) FTIR spectra of TA and Au@TA. (b) Number-based hydrodynamic size distributions by DLS. (c) ζ-potential of Au@TA and Au@TA-OGP showing a modest shift toward neutrality after peptide assembly. (d) TEM images of spherical, well-dispersed cores (left; scale bar, 100 nm) with a magnified single particle (right; scale bar, 10 nm). (e) TEM-derived size histogram. (f) UV-Vis spectrum of Au@TA (black line) and Au@TA-OGP (red line). (g) One-month stability of dispersions at room temperature without visible change.

Fig. 3. (a) In vitro biosafety of Au@TA-OGP. (b and c) Hemolysis ratios of different Au@TA-OGP concentrations incubated with RBCs. (d) RAW264.7 cell viability by MTT assay. (e) HUVEC live/dead staining (Calcein-AM/PI) in control, Au@TA, or Au@TA-OGP.

Fig. 4. Cellular uptake and in vitro osteogenesis enhanced by Au@TA-OGP. (a) Experimental timeline for nanoparticle exposure and osteogenic induction with readouts of AuNP uptake (by CLSM) and mineralization (ARS staining). (b) Confocal images of RAW264.7 cells incubated with Cy5-labeled Au@TA-OGP. (c and d) Calcium deposition by MC3T3-E1 cells cultured with Control, Au@TA, or Au@TA-OGP, assessed by ARS. Quantitative data are presented as the mean±SD. Error bars indicate standard deviation. *p < 0.05.

Fig. 5. (a) Overview of the treatment protocol. (b) HE staining of the gastrocnemius muscle; Masson’s trichrome staining of the gastrocnemius muscle. (c) Representative TEM images of regenerated nerves. (d) Average percentage of muscle fiber area. (e) Average percentage of collagen fiber area. (f) Quantification of myelin sheath thickness. (g) Statistical analysis of the number of myelinated axons. Error bars indicate standard deviation. *p < 0.05.

Fig. 6. (a) Treatment effects of different groups in alleviating in vivo bone loss in an OVX mice. (b) Representative micro-CT images showing the two- and three-dimensional microarchitectures of trabeculae in the distal femurs of mice. (c) Representative images of tibial sections stained with TRAP and H&E. (d-g) trabecular thickness (Tb.Th), Percent bone volume (BV/TV), trabecular separation (Tb.Sp) and trabecular number (Tb.N) as measured by micro-CT.

Fig. 7. Biosafety of Au@TA-OGP in OVX mice. (a) Histological evaluation of the heart, liver, spleen, lung, and kidney for in vivo biodistribution and metabolic assessment. Scale bar = 50 µm. (b-d) Serum levels of ALT, AST, and ALP at the end of the study. Data are presented as mean ± SD (n = 6).

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