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<p>Contemporary cancer therapies encounter fundamental obstacles such as resistance development, systemic toxicity thresholds, inadequate tumor discrimination, and restricted treatment efficacy ranges.&#xa0;To synthesize biogenic Ag/MgO nanocomposite using marine bacterium <i>Bacillus tequilensis</i> MYG163 exopolysaccharide and evaluate its multifunctional therapeutic properties.&#xa0;Ag/MgO nanocomposite was synthesized via bacterial EPS-mediated biogenic route and characterized by UV-Vis, FT-IR, TEM, XRD, EDX, DLS, and zeta potential. Hemocompatibility, antioxidant capacity (DPPH, ABTS<sup>•+</sup>), anti-inflammatory activity (COX-1/COX-2 inhibition), and cytotoxicity against WI38 fibroblasts and four cancer cell lines, HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), HeLa (cervical cancer), and PC-3 (prostate cancer) were evaluated. Apoptotic mechanisms were examined through qRT-PCR, comet assay, diphenylamine assay, and flow cytometry.&#xa0;Biogenic synthesis using <i>B. tequilensis</i> MYG163 EPS yielded spherical Ag/MgO nanocomposite (10–50&#xa0;nm), negative surface charge (-26.8 mV), hydrodynamic size of 56.8&#xa0;nm containing 29.6 wt% silver and 8.8 wt% magnesium with face-centered cubic silver reflections and cubic periclase MgO structure. XRD confirmed crystalline phases at 38.04°, 43.32°, 62.65° (Ag) and 59.27°, 75.05° (MgO). Hemolysis remained ≤ 1.6% at 1000&#xa0;µg/mL. Antioxidant IC₅₀: 22.22&#xa0;µg/mL (DPPH), 17.38&#xa0;µg/mL (ABTS<sup>•+</sup>). Anti-inflammatory IC₅₀: 110.67&#xa0;µg/mL (COX-1), 167.47&#xa0;µg/mL (COX-2). Cancer cell IC₅₀ ranged 61.12–149.51&#xa0;µg/mL vs. 369.53&#xa0;µg/mL (WI38). HepG2 treatment triggered p53 (378%), p21 (487%), Bax (297%), Caspase-3 (654%) upregulation, Bcl-2 (64%) downregulation, DNA damage (73% increase), S-phase arrest (42.80%), and G2/M block (8.35%).&#xa0;Bacterial EPS enables single-step synthesis of biocompatible Ag/MgO nanocomposite with integrated antioxidant, anti-inflammatory, and cancer-selective apoptotic properties, offering potential for targeted therapy development.</p>

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Multifunctional Ag/MgO Nanocomposite from Marine Bacterium Bacillus tequilensis MYG163 EPS Triggers Metalloptosis in HepG2 Cells Through p53-Mediated DNA Damage and Caspase-3 Activation

  • 期刊论文

  • 发表日期：

    2026年2月7日

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  • Anes A. Al-Sharqi,
  • Mohamed E. Eissa,
  • Rana Hussein Naser,
  • Zahraa Falah Azeez,
  • Aisha M. A. Shahlol,
  • Zinab Alatawi,
  • Tarek A. Yousef,
  • Ibrahim M. Ibrahim,
  • Faisal Miqad K. Albaqami,
  • Mohamed Abdel-Megid,
  • Enji M. Hammad,
  • Ahmed Ghareeb

摘要

Contemporary cancer therapies encounter fundamental obstacles such as resistance development, systemic toxicity thresholds, inadequate tumor discrimination, and restricted treatment efficacy ranges. To synthesize biogenic Ag/MgO nanocomposite using marine bacterium Bacillus tequilensis MYG163 exopolysaccharide and evaluate its multifunctional therapeutic properties. Ag/MgO nanocomposite was synthesized via bacterial EPS-mediated biogenic route and characterized by UV-Vis, FT-IR, TEM, XRD, EDX, DLS, and zeta potential. Hemocompatibility, antioxidant capacity (DPPH, ABTS•+), anti-inflammatory activity (COX-1/COX-2 inhibition), and cytotoxicity against WI38 fibroblasts and four cancer cell lines, HepG2 (hepatocellular carcinoma), MCF-7 (breast cancer), HeLa (cervical cancer), and PC-3 (prostate cancer) were evaluated. Apoptotic mechanisms were examined through qRT-PCR, comet assay, diphenylamine assay, and flow cytometry. Biogenic synthesis using B. tequilensis MYG163 EPS yielded spherical Ag/MgO nanocomposite (10–50 nm), negative surface charge (-26.8 mV), hydrodynamic size of 56.8 nm containing 29.6 wt% silver and 8.8 wt% magnesium with face-centered cubic silver reflections and cubic periclase MgO structure. XRD confirmed crystalline phases at 38.04°, 43.32°, 62.65° (Ag) and 59.27°, 75.05° (MgO). Hemolysis remained ≤ 1.6% at 1000 µg/mL. Antioxidant IC₅₀: 22.22 µg/mL (DPPH), 17.38 µg/mL (ABTS•+). Anti-inflammatory IC₅₀: 110.67 µg/mL (COX-1), 167.47 µg/mL (COX-2). Cancer cell IC₅₀ ranged 61.12–149.51 µg/mL vs. 369.53 µg/mL (WI38). HepG2 treatment triggered p53 (378%), p21 (487%), Bax (297%), Caspase-3 (654%) upregulation, Bcl-2 (64%) downregulation, DNA damage (73% increase), S-phase arrest (42.80%), and G2/M block (8.35%). Bacterial EPS enables single-step synthesis of biocompatible Ag/MgO nanocomposite with integrated antioxidant, anti-inflammatory, and cancer-selective apoptotic properties, offering potential for targeted therapy development.