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Войти в исследования Biomaterials advances · 2026
PEGylated fucoxanthin liposomes remodel G0/G1 cell cycle homeostasis and suppress gallbladder cancer progression via modulation of NR2F1-mediated signaling networks.
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Cao Jun-Feng, Hang Kuan, Zhang Xiao, Xia Qingjie, Xia Zengliang, Liao Dunshui, Rong Cheng, Li Kezhou
Аннотация
PURPOSE: Gallbladder cancer (GBC) is a highly aggressive and refractory biliary malignancy with disordered proliferative homeostasis, rapid malignant progression and scarce effective clinical therapies. Marine fucoxanthin possesses prominent anti-tumor activity, whereas its poor water solubility and low bioavailability limit application, and its core biomolecular mechanism against GBC remains poorly clarified. This study aimed to construct PEGylated fucoxanthin liposomes and elucidate their anti-tumor mechanism targeting biomolecular dynamics and core regulatory targets in GBC.
METHODS: The anti-proliferative, anti-migratory, pro-apoptotic and cell cycle-regulatory effects of fucoxanthin-liposomes were verified using 2D monolayer and physiologically biomimetic 3D GBC spheroid models. Integrative transcriptomic analysis, multi-algorithm machine learning screening, RT-qPCR and immunofluorescence validation were performed to screen core functional targets. Molecular docking and 100 ns molecular dynamics simulations were further conducted to confirm the stable binding characteristics between fucoxanthin and the target protein.
RESULTS: Fucoxanthin-liposomes exerted significant dose-dependent inhibitory effects on GBC proliferation and migration, induced mitochondrial structural damage, extensive cell apoptosis, and robust G0/G1 cell cycle arrest. Multi-omics combined with machine learning identified NR2F1 as the pivotal target, whose expression was markedly upregulated after fucoxanthin-liposomes treatment. Fucoxanthin could stably bind NR2F1 through hydrogen bonding and hydrophobic interactions with excellent thermodynamic stability.
CONCLUSION: PEGylated fucoxanthin liposomes restored G0/G1 quiescence-dominated cellular homeostasis and reversed pathological proliferative imbalance in GBC via transcriptional activation of NR2F1. Upregulated NR2F1 remodeled tumor proliferative homeostasis by hierarchically modulating PI3K/AKT/mTOR and JAK2/STAT3 signaling networks, and ultimately restrained GBC clonal proliferation and invasive progression.
METHODS: The anti-proliferative, anti-migratory, pro-apoptotic and cell cycle-regulatory effects of fucoxanthin-liposomes were verified using 2D monolayer and physiologically biomimetic 3D GBC spheroid models. Integrative transcriptomic analysis, multi-algorithm machine learning screening, RT-qPCR and immunofluorescence validation were performed to screen core functional targets. Molecular docking and 100 ns molecular dynamics simulations were further conducted to confirm the stable binding characteristics between fucoxanthin and the target protein.
RESULTS: Fucoxanthin-liposomes exerted significant dose-dependent inhibitory effects on GBC proliferation and migration, induced mitochondrial structural damage, extensive cell apoptosis, and robust G0/G1 cell cycle arrest. Multi-omics combined with machine learning identified NR2F1 as the pivotal target, whose expression was markedly upregulated after fucoxanthin-liposomes treatment. Fucoxanthin could stably bind NR2F1 through hydrogen bonding and hydrophobic interactions with excellent thermodynamic stability.
CONCLUSION: PEGylated fucoxanthin liposomes restored G0/G1 quiescence-dominated cellular homeostasis and reversed pathological proliferative imbalance in GBC via transcriptional activation of NR2F1. Upregulated NR2F1 remodeled tumor proliferative homeostasis by hierarchically modulating PI3K/AKT/mTOR and JAK2/STAT3 signaling networks, and ultimately restrained GBC clonal proliferation and invasive progression.