ArticleBiomaterials research2026
Resveratrol-Loaded Responsive Core-Shell Tecto Dendrimers Potentiate Hepatocellular Carcinoma Therapy.
Article in Biomaterials research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
10 authors.
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Abstract
Hepatocellular carcinoma (HCC) exhibits profound metabolic reprogramming, particularly enhanced glycolytic activity, which represents a therapeutic vulnerability. However, the remarkable adaptability of HCC metabolism allows tumor cells to compensate for metabolic disturbances and preserve cellular homeostasis, reducing the effectiveness of metabolism-targeted strategies. Therefore, strategies sustaining metabolic perturbation beyond tumor adaptive capacity are needed. Herein, we developed a pH-responsive zwitterion-modified core-shell tecto dendrimer nanocarrier (CSTD-PS) for resveratrol (Res) delivery to overcome these limitations and potentiate HCC therapy. CSTD-PS was constructed through dynamic boronate ester-mediated assembly and zwitterionic surface modification, enabling Res encapsulation and pH-responsive release. After Res encapsulation, Res@CSTD-PS exhibited enhanced cellular uptake and nanocarrier-associated tumor localization, resulting in superior antitumor efficacy in HCC models compared with free Res. Mechanistically, Res@CSTD-PS suppressed glycolytic regulators, including hexokinase 2, glucose transporter 1, and pyruvate kinase M2, accompanied by enhanced stress responses (glucose-regulated protein 78 and nuclear factor erythroid 2-related factor 2) and p53/caspase-3-associated apoptotic signaling. Res@CSTD-PS also reduced programmed death-ligand 1 expression, suggesting potential attenuation of immune-evasive characteristics. Collectively, this study introduces a strategy enabled by intelligent dendrimer-based nanomedicine, providing a promising approach for enhancing natural compound-based therapy against HCC.
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Registered trials
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