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<p>Genistein (GSN) demonstrates various therapeutic actions in cancers, nevertheless, poor bioavailability with low aqueous solubility limits its clinical application. In this work, GSN was fabricated into GSN nanocrystals (GNCs), and adsorbed on the silver nanoparticles (AgNPs). Further to enhance tumor targeting, an additional coating of Hyaluronic Acid (HA), was provided to the AgNP03:GNC nanoparticles to obtain HA coated nanocarrier (HA-AgNP03:GNC). The fabricated HA-AgNP03:GNC exhibited a particle size (318.5±1.73&#xa0;nm), zeta potential (− 49.5±1.57 mV), PdI (0.289±0.07), with high adsorption efficiency (99.86± 0.05%) and drug loading capacity (12.29 ± 0.24%). The saturation solubility studies of HA-AgNP03:GNC were performed in triplicate, with results reported in mean ± S.D. The HA-AgNP03:GNC showed enhancement (45.82 ± 0.12&#xa0;µg/mL) in solubility compared to pure GSN (1.46 ± 0.03&#xa0;µg/mL), and displayed a controlled release pattern with non-Fickian diffusion. The qualitative (fluorescence microscopy) and quantitative (fluorometric) analysis uncovered the cellular uptake mechanism attributed to CD44 receptor–mediated via HA shell. Furthermore, the HA-AgNP03:GNC exhibited enhanced cytotoxicity (IC<sub>50</sub> = 24.76&#xa0;µg/mL, <i>p</i> &lt; 0.0001), and apoptosis (19.45 ± 2.19%, <i>p</i> &lt; 0.0001) in A375 cells. The in-vivo efficacy was evaluated in A375 tumor-bearing mice model and revealed HA-AgNP03:GNC showed slowest tumor growth with tumor volume of 1772.50 ± 313.70 mm<sup>3</sup>, <i>p</i> &lt; 0.01 compared to the untreated cohort (2580.0 ± 200.00 mm<sup>3</sup>). Therefore, our results indicate promising potential of HA-AgNP03:GNC nanoplatform in drug delivery of GSN for melanoma treatment, however, its effectiveness requires further comprehensive preclinical and clinical evaluation.</p> Graphical Abstract <p></p>

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Hyaluronic Acid Surface Engineered Multi-nanoparticulate System of Silver Nanoparticles Adsorbed Genistein Nanocrystals in Melanoma

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Bhagyashree V. Salvi,
  • Pravin Shende

摘要

Genistein (GSN) demonstrates various therapeutic actions in cancers, nevertheless, poor bioavailability with low aqueous solubility limits its clinical application. In this work, GSN was fabricated into GSN nanocrystals (GNCs), and adsorbed on the silver nanoparticles (AgNPs). Further to enhance tumor targeting, an additional coating of Hyaluronic Acid (HA), was provided to the AgNP03:GNC nanoparticles to obtain HA coated nanocarrier (HA-AgNP03:GNC). The fabricated HA-AgNP03:GNC exhibited a particle size (318.5±1.73 nm), zeta potential (− 49.5±1.57 mV), PdI (0.289±0.07), with high adsorption efficiency (99.86± 0.05%) and drug loading capacity (12.29 ± 0.24%). The saturation solubility studies of HA-AgNP03:GNC were performed in triplicate, with results reported in mean ± S.D. The HA-AgNP03:GNC showed enhancement (45.82 ± 0.12 µg/mL) in solubility compared to pure GSN (1.46 ± 0.03 µg/mL), and displayed a controlled release pattern with non-Fickian diffusion. The qualitative (fluorescence microscopy) and quantitative (fluorometric) analysis uncovered the cellular uptake mechanism attributed to CD44 receptor–mediated via HA shell. Furthermore, the HA-AgNP03:GNC exhibited enhanced cytotoxicity (IC50 = 24.76 µg/mL, p < 0.0001), and apoptosis (19.45 ± 2.19%, p < 0.0001) in A375 cells. The in-vivo efficacy was evaluated in A375 tumor-bearing mice model and revealed HA-AgNP03:GNC showed slowest tumor growth with tumor volume of 1772.50 ± 313.70 mm3, p < 0.01 compared to the untreated cohort (2580.0 ± 200.00 mm3). Therefore, our results indicate promising potential of HA-AgNP03:GNC nanoplatform in drug delivery of GSN for melanoma treatment, however, its effectiveness requires further comprehensive preclinical and clinical evaluation.

Graphical Abstract