Multifunctional And Stimuli-Responsive Polydopamine Nanoparticle-Based Platform For Targeted Antimicrobial Applications

The rising threat of antimicrobial resistance is a crisis of a global scale. If not addressed, it can lead to health care system problems worldwide. This warrants alternative therapeutic approaches whose mechanism of action starkly differs from conventional antibiotic-based therapies. Here, a multifunctional and stimuli-responsive (NIR laser-activated) antimicrobial platform is engineered by combining the intrinsic photothermal capability and excellent biocompatibility of polydopamine nanoparticles (PdNPs), with the membrane targeting and lytic activities of an antimicrobial peptide (AMP). The resulting PdNP-AMP nanosystem can specifically target and destabilize the mechanical integrity of the outer membrane ofEscherichia coli, as measured using the atomic force microscope. Furthermore, the laser-induced nano-localized heating of PdNP-in close proximity to the already compromised bacterial envelope-induces further membrane damage. This results in a more efficient, laser-activated, bacterial killing action of PdNP-AMP. The antimicrobial platform developed in this work is shown to be effective against a drug-resistantE. coli. Overall, this work highlights the advantage and strength of combining multiple and coordinated biocidal mechanisms, into one nanomaterial-based system and its promise in treating drug-resistant pathogens.