Stimuli-Responsive Copper Modified Mesoporous Silica Nanoparticles as Smart Antimicrobial Delivery System for Antimicrobial Applications.
Abstract
The emergence of multidrug-resistant pathogens poses a significant challenge to conventional antimicrobial therapies and underscores the urgent need for innovative therapeutic strategies using highly efficacious and less toxic antimicrobial compounds, as well as more targeted antimicrobial delivery strategies to prevent uncontrolled release, which contributes to the rise of drug resistance. In this study, the design and synthesis of copper-modified mesoporous silica nanoparticles (Cu-MSNs) were described as a stimuli-responsive, smart antimicrobial delivery system incorporating carvacrol as a bioactive alternative to conventional antibiotics. The Cu-MSNs exhibit high surface area, tunable pore size, and efficient carvacrol loading. Copper ions embedded within the silica matrix provide intrinsic antimicrobial activity and may enhance the antimicrobial effect of carvacrol. Poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) brushes were anchored on Cu-MSNs via surface-initiated atom transfer radical polymerization (SI-ATRP). The PDMAEMA brushes provided stimuli-responsive behavior, enabling pH- and temperature-dependent modulation of carvacrol release. The successful synthesis of Cu-MSN-PDMAEMA has been confirmed by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), elemental analysis (EA), and transmission electron microscopy (TEM). Moreover, stimuli-responsive behavior was confirmed using dynamic light scattering (DLS) experiments, demonstrating the pH- and temperature-dependent response of the PDMAEMA brushes. Finally, the carvacrol release behavior was studied at different pH values by using a sensitive paper-based electrochemical sensor. The multifunctional nanoplatform exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria as well as antiviral activity against representative enveloped and non-enveloped viral models. This synergistic design combines the benefits of a natural antimicrobial agent, intrinsic metallic activity, and smart polymer regulation, offering an strategy to enhance efficacy while minimizing off-target effects. Release studies demonstrated pH-triggered carvacrol delivery, with enhanced release under acidic conditions, confirming the gating function of the PDMAEMA brushes, highlighting the potential of these particles as an antibiotic-free alternative for preventing microbial infections while mitigating the development of antimicrobial resistance (AMR).
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