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<p>The in vitro studies revealed that the fisetin (FT) possessed strong anti-cancer activity against cancer cells. however, it was hampered by the low solubility and bioavailability of the compound within the cells. Therefore, to address the limitation, Nanoparticles (NPs) made up of CHI and CS alone, along with CHI and CS with lecithin were fabricated through the process of ionic gelation. NPs were optimized through conductometric and potentiometric titrations and thoroughly characterized using high-resolution transmission electron microscopy (HR-TEM), high-resolution scanning electron microscopy (HR-SEM), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET) surface analysis, atomic force microscopy (AFM), and fluorescence spectroscopy. The resulting NPs exhibited spherical morphology with diameters ranging from 90.0 ± 5.0&#xa0;nm (CHI/CS/FT) to 130 ± 4.0&#xa0;nm (CHI/CS/Lecithin/FT) and having positive zeta potential of + 27.4 ± 1.4&#xa0;mV, suggesting favorable colloidal stability. Lecithin incorporation significantly improved encapsulation efficiency from 68.4 ± 2.1% (CHI/CS/FT) to 88.7 ± 1.8% (CHI/CS/Lecithin/FT) (<i>p</i> &lt; 0.001), while also enhancing surface smoothness and porosity (BET surface area increased by 23%). In vitro release studies demonstrated a biphasic pattern, with an initial burst (42% in 8&#xa0;h), followed by sustained release to 84.3 ± 2.5% over 72&#xa0;h at physiological pH (7.4) for lecithin modified NPs. The CHI/CS/Lecithin/FT formulation exhibited markedly higher cytotoxicity compared to free FT and CHI/CS/FT groups. At 80&#xa0;μM, cytotoxicity reached 80.2% (<i>p</i> &lt; 0.0001), indicating significantly enhanced anticancer efficacy. This superior activity was associated with mitochondrial membrane depolarization and apoptotic nuclear alterations, suggesting that lecithin incorporation substantially improves cellular uptake, therapeutic performance, and overall efficacy of the nanoparticle-based drug delivery system.</p>

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Role of Lecithin in Modulating Fisetin Release, Mitochondrial Membrane Depolarization Anticancer Activity, and Mitochondrial Dysfunction in Biopolymer NPs

  • 期刊论文

  • 发表日期：

    2026年7月11日

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  • Satyam Sharma,
  • Raghuraj Singh,
  • Rajat Mudgal,
  • Sairam Krishnamurthy,
  • Rahul Kumar Verma,
  • Sanjiv Singh

摘要

The in vitro studies revealed that the fisetin (FT) possessed strong anti-cancer activity against cancer cells. however, it was hampered by the low solubility and bioavailability of the compound within the cells. Therefore, to address the limitation, Nanoparticles (NPs) made up of CHI and CS alone, along with CHI and CS with lecithin were fabricated through the process of ionic gelation. NPs were optimized through conductometric and potentiometric titrations and thoroughly characterized using high-resolution transmission electron microscopy (HR-TEM), high-resolution scanning electron microscopy (HR-SEM), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET) surface analysis, atomic force microscopy (AFM), and fluorescence spectroscopy. The resulting NPs exhibited spherical morphology with diameters ranging from 90.0 ± 5.0 nm (CHI/CS/FT) to 130 ± 4.0 nm (CHI/CS/Lecithin/FT) and having positive zeta potential of + 27.4 ± 1.4 mV, suggesting favorable colloidal stability. Lecithin incorporation significantly improved encapsulation efficiency from 68.4 ± 2.1% (CHI/CS/FT) to 88.7 ± 1.8% (CHI/CS/Lecithin/FT) (p < 0.001), while also enhancing surface smoothness and porosity (BET surface area increased by 23%). In vitro release studies demonstrated a biphasic pattern, with an initial burst (42% in 8 h), followed by sustained release to 84.3 ± 2.5% over 72 h at physiological pH (7.4) for lecithin modified NPs. The CHI/CS/Lecithin/FT formulation exhibited markedly higher cytotoxicity compared to free FT and CHI/CS/FT groups. At 80 μM, cytotoxicity reached 80.2% (p < 0.0001), indicating significantly enhanced anticancer efficacy. This superior activity was associated with mitochondrial membrane depolarization and apoptotic nuclear alterations, suggesting that lecithin incorporation substantially improves cellular uptake, therapeutic performance, and overall efficacy of the nanoparticle-based drug delivery system.