<p>In this study, pH-responsive chitosan-coated selenium nanoparticles (MT-SeNPs@Ch) were green-synthesized using <i>Morinda tinctoria</i> leaf extract and evaluated for their antifungal, antimycotoxin, anticancer, and nanotoxicological properties. LC-MS/MS-QTOF analysis of the leaf extract identified 23 phytochemical constituents, predominantly phenolic acids and flavonoids, which facilitated the bioreduction and stabilization of selenium nanoparticles (SeNPs). The synthesized SeNPs were amorphous and quasi-spherical with a core size of ~ 27&#xa0;nm, which increased to ~ 35&#xa0;nm after chitosan coating, while the hydrodynamic diameter increased from ~ 80–90&#xa0;nm to ~ 110–130&#xa0;nm. Chitosan functionalization reversed the surface charge from − 28 to + 48 mV, imparting strong pH-responsive stability under acidic conditions. MT-SeNPs@Ch exhibited pronounced pH-dependent antifungal activity against <i>Aspergillus ochraceus</i>, with the lowest MIC (23.81 ± 0.40&#xa0;µg/mL) and MFC (29.07 ± 0.61&#xa0;µg/mL) at pH 5 compared to pH 6 and 7, accompanied by strong inhibition of spore germination, elevated intracellular ROS generation, near-complete ergosterol depletion, and significant suppression of ochratoxin A (OTA) production. In mammalian cell models, nonlinear dose–response analysis yielded an IC₅₀ of 44.29 ± 1.34&#xa0;µg/mL for MDA-MB-231 cancer cells and 80.62 ± 2.66&#xa0;µg/mL for HEK-293 normal cells, resulting in a favorable Selectivity Index (SI = 1.82) and Therapeutic Index (TI = 3.41), indicating preferential cytotoxicity toward cancer cells and a useful therapeutic window. Zebrafish embryo toxicity assays established a no-observed-effect concentration (NOEC) of 150&#xa0;µg/mL and a lowest-observed-effect concentration (LOEC) of 175&#xa0;µg/mL, demonstrating that toxicological thresholds in non-target systems were substantially higher than the fungicidal concentrations. Collectively, this study introduces a <i>Morinda tinctoria</i>-mediated nanoarchitectonic strategy for engineering pH-responsive chitosan–selenium nanoplatforms that selectively target mycotoxigenic fungi under acidic microenvironments while maintaining favorable biocompatibility, thereby advancing the development of next-generation stimuli-responsive nanomaterials for food safety, mycotoxin mitigation, and translational biomedical applications.</p>

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Morinda tinctoria-Mediated Nanoarchitectonics of pH-Responsive Chitosan-Coated Selenium Nanoplatforms for Targeted and Biocompatible Suppression of Aspergillus ochraceus and Ochratoxin A

  • Anusuya Nagaraj,
  • Sudhakar Poda,
  • Ushakiranmayi Mangamuri,
  • Vinay Viswanath Konduri,
  • Balantrapu Sriram,
  • Lokanadhan Gunti,
  • Pranab Kumar Mahata,
  • Shaurya Dev Ganguly,
  • Sakshi Pandey,
  • Srikrishnan Rajendran Sriramkumar,
  • Naveen Kumar Kalagatur

摘要

In this study, pH-responsive chitosan-coated selenium nanoparticles (MT-SeNPs@Ch) were green-synthesized using Morinda tinctoria leaf extract and evaluated for their antifungal, antimycotoxin, anticancer, and nanotoxicological properties. LC-MS/MS-QTOF analysis of the leaf extract identified 23 phytochemical constituents, predominantly phenolic acids and flavonoids, which facilitated the bioreduction and stabilization of selenium nanoparticles (SeNPs). The synthesized SeNPs were amorphous and quasi-spherical with a core size of ~ 27 nm, which increased to ~ 35 nm after chitosan coating, while the hydrodynamic diameter increased from ~ 80–90 nm to ~ 110–130 nm. Chitosan functionalization reversed the surface charge from − 28 to + 48 mV, imparting strong pH-responsive stability under acidic conditions. MT-SeNPs@Ch exhibited pronounced pH-dependent antifungal activity against Aspergillus ochraceus, with the lowest MIC (23.81 ± 0.40 µg/mL) and MFC (29.07 ± 0.61 µg/mL) at pH 5 compared to pH 6 and 7, accompanied by strong inhibition of spore germination, elevated intracellular ROS generation, near-complete ergosterol depletion, and significant suppression of ochratoxin A (OTA) production. In mammalian cell models, nonlinear dose–response analysis yielded an IC₅₀ of 44.29 ± 1.34 µg/mL for MDA-MB-231 cancer cells and 80.62 ± 2.66 µg/mL for HEK-293 normal cells, resulting in a favorable Selectivity Index (SI = 1.82) and Therapeutic Index (TI = 3.41), indicating preferential cytotoxicity toward cancer cells and a useful therapeutic window. Zebrafish embryo toxicity assays established a no-observed-effect concentration (NOEC) of 150 µg/mL and a lowest-observed-effect concentration (LOEC) of 175 µg/mL, demonstrating that toxicological thresholds in non-target systems were substantially higher than the fungicidal concentrations. Collectively, this study introduces a Morinda tinctoria-mediated nanoarchitectonic strategy for engineering pH-responsive chitosan–selenium nanoplatforms that selectively target mycotoxigenic fungi under acidic microenvironments while maintaining favorable biocompatibility, thereby advancing the development of next-generation stimuli-responsive nanomaterials for food safety, mycotoxin mitigation, and translational biomedical applications.