Increasing prevalence of antibiotic resistance presents a global health crisis. Gram-negative bacteria, in particular are resistant to a wide range of drugs due to their specialized outer membranes. Enediyne natural products have exhibited remarkable potency against biological cells. Their potency comes from Bergman cyclization of the enediyne core that generates reactive diradical species and can be triggered by a heat stimulus. Plasmonic gold nanoparticles have the capability of converting irradiated light into heat via non radiative properties. Gold nanorods (AuNRs) can be tuned to strongly absorb near-infrared (NIR) radiation which lies in the biological transparency window. We have shown that octa-4-en-2,6-diyne-1,8-diamine (EDDA) molecules functionalized on AuNR surface can be activated to generate diradical species through NIR irradiation of nanorods. In order to localize the nanorods on bacterial cells, we also coated our AuNRs with Polymyxin B nonapeptide (PMBN), a cationic cyclic peptide that specifically targets the lipopolysaccharide component of the outer membrane of Gram-negative pathogens. We have explored our strategy by treating DH5a strain of <i>Escherichia coli </i>with our bifunctional AuNRs. We find that, following attachment of nanorods to DH5a, NIR laser irradiation results in a significant reduction in the viability of bacterial cells. We identify that the photothermal heat generation of nanorods and reactive diradical generation by EDDA both contribute towards DH5a cell death.

Bifunctional near-infrared light responsive gold nanorods for phototherapy of gram-negative <i>Escherichia coli</i>

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Bifunctional near-infrared light responsive gold nanorods for phototherapy of gram-negative Escherichia coli