Hybrid Nanostructures of Bio-Actives and Metal Nanoparticles: A New Frontier in Combating Antimicrobial Resistance

The bioactive compound-capped metal nanoparticles (MNPs) synthesis has gained significance as a
rationally designed approach to enhance antimicrobial activity against the multidrug-resistant
pathogens. Though bioactive molecules have unique biological activity, MNPs such as silver, zinc
oxide and copper possess physiochemical properties like high surface reactivity, ROS production,
membrane permeability, etc. Together, these hybrid systems show an emergence of combined action
mechanisms such as improved cell uptake, targeted membrane disruption, higher oxidative stress and
blockage of crucial metabolic and genetic activities. Functionalization of the MNP surface with
natural compounds, phytochemicals, peptides, or antibiotics also improves stability, biocompatibility,
and controlled release, allowing the use of lower effective doses while reducing toxicity. Studies have
shown that hybrid nanomedicines are superior to individual components and exhibit broad-spectrum
activity against Gram-positive and Gram-negative bacteria, biofilms, and resistant strains. Hence, this
review discusses about bioactive compounds and metal nanoparticles individually and its integrative
formulations as an effective multitarget antimicrobial strategy with great potential for therapeutic,
biomedical, and environmental applications.