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<p>The concurrent challenges of multidrug-resistant (MDR) biofilms and the indiscriminate toxicity of conventional chemotherapeutics demand the development of selective, multifunctional nanomedicines. To address this, we phytofabricated <i>Cinnamomum cassia</i>-engineered silver nanoparticles (Cin-AgNPs) and hypothesized that their bioactive phytochemical corona dictates a multi-targeted mechanism: competitively inhibiting bacterial biofilm adhesion, selectively triggering cancer cell apoptosis, and providing a cytoprotective ‘ROS shield’ to normal tissues. Physicochemical characterization confirmed the formation of spherical nanoparticles with a metallic core size of 38–55 nm and a fully hydrated corona (hydrodynamic diameter: 70–90 nm). The nanohybrids exhibited robust colloidal stability (zeta potential: -30.9 mV) over 30 days. Crucially, ICP-MS analysis confirmed a pH-responsive Ag<sup>+</sup> release profile: minimal release at physiological pH (15.6%) supporting the cytoprotective ‘ROS Shield’, paired with a rapid burst release (68.7%) in acidic environments driving a targeted ‘Trojan Horse’ attack. Biological evaluations revealed potent broad-spectrum antimicrobial activity, most notably against spore-forming <i>Bacillus cereus</i> (MIC: 6.25&#xa0;µg/mL), and an 82% reduction in <i>Staphylococcus aureus</i> biofilm biomass. Selective cytotoxicity was demonstrated against Triple-Negative Breast Cancer (MDA-MB-231) cells (IC<sub>50</sub>: 102.4&#xa0;µg/mL) while maintaining high viability (&gt; 93%) in normal Vero kidney cells (IC<sub>50</sub> &gt; 4000&#xa0;µg/mL) yielding an in vitro Selectivity Index of ≈ 40. Molecular docking simulations provided a predictive structural rationale, revealing that surface-bound eugenol and <i>trans</i>-cinnamaldehyde effectively block the catalytic groove of bacterial Sortase A and the anti-apoptotic pocket of Bcl-2. Furthermore, high-affinity interactions with the human Keap1 domain suggest a mechanism for the antioxidant shield in healthy cells. Ultimately, this study establishes Cin-AgNPs as a mechanistically defined, multi-targeted platform demonstrating promising foundational efficacy that warrants rigorous in vivo preclinical validation.</p>

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Mechanistic Evaluation of Cinnamomum cassia-Engineered Silver Nanoparticles Against Triple-Negative Breast Cancer and Biofilm-Forming Bacteria

  • 期刊论文

  • 发表日期：

    2026年5月29日

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  • Niketan Deshmukh,
  • Naqvi Hadisha

摘要

The concurrent challenges of multidrug-resistant (MDR) biofilms and the indiscriminate toxicity of conventional chemotherapeutics demand the development of selective, multifunctional nanomedicines. To address this, we phytofabricated Cinnamomum cassia-engineered silver nanoparticles (Cin-AgNPs) and hypothesized that their bioactive phytochemical corona dictates a multi-targeted mechanism: competitively inhibiting bacterial biofilm adhesion, selectively triggering cancer cell apoptosis, and providing a cytoprotective ‘ROS shield’ to normal tissues. Physicochemical characterization confirmed the formation of spherical nanoparticles with a metallic core size of 38–55 nm and a fully hydrated corona (hydrodynamic diameter: 70–90 nm). The nanohybrids exhibited robust colloidal stability (zeta potential: -30.9 mV) over 30 days. Crucially, ICP-MS analysis confirmed a pH-responsive Ag+ release profile: minimal release at physiological pH (15.6%) supporting the cytoprotective ‘ROS Shield’, paired with a rapid burst release (68.7%) in acidic environments driving a targeted ‘Trojan Horse’ attack. Biological evaluations revealed potent broad-spectrum antimicrobial activity, most notably against spore-forming Bacillus cereus (MIC: 6.25 µg/mL), and an 82% reduction in Staphylococcus aureus biofilm biomass. Selective cytotoxicity was demonstrated against Triple-Negative Breast Cancer (MDA-MB-231) cells (IC50: 102.4 µg/mL) while maintaining high viability (> 93%) in normal Vero kidney cells (IC50 > 4000 µg/mL) yielding an in vitro Selectivity Index of ≈ 40. Molecular docking simulations provided a predictive structural rationale, revealing that surface-bound eugenol and trans-cinnamaldehyde effectively block the catalytic groove of bacterial Sortase A and the anti-apoptotic pocket of Bcl-2. Furthermore, high-affinity interactions with the human Keap1 domain suggest a mechanism for the antioxidant shield in healthy cells. Ultimately, this study establishes Cin-AgNPs as a mechanistically defined, multi-targeted platform demonstrating promising foundational efficacy that warrants rigorous in vivo preclinical validation.