Photo-responsive functional gold nanocapsules for inactivation of community-acquired, highly virulent, multidrug-resistant MRSA

The indiscriminate and sporadic use of antibiotics has contributed to the emergence of drug resistance phenomenon in bacteria including but not limited to Staphylococcus aureus. These drug-resistant bacteria have been threatening safety in hospitals and adversely affecting human health. Here we report a strategy to design photo-stimulated theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) superbug USA300. The nanocapsule probe is based on gold nanorods (GNRs) coated with pegylated thiol, mPEG-SH, which has been further modified by adding successively a natural antibacterial compound such as curcumin, and a cell targeting deoxyribonucleic acid (DNA) aptamer. We have used this novel gold nanocapsules for near-infrared (NIR) photophysical stimulation against pathogenic bacteria. We have found that the novel nanocapsule blocks biofilm formation and kills bacteria by photothermal action that causes disruption of the bacterial cell wall and membrane. In this approach, multiple drug-resistant Staphylococcus aureus has been captured by these nanocapsules through DNA aptamer targeting. All of the trapped bacteria could be killed in 30 minutes during the NIR stimulation due to the combination of photothermal effect, the generation of reactive oxygen species (ROS) and a loss of transmembrane potential (Delta psi). Importantly we did not notice any resistance developed against the photothermal treatment. This is remarkable from an anti-biofilm activity point of view. Importantly, these multifunctional nanocapsules have also shown a surface enhanced Raman spectroscopy (SERS) effect, which could be used to evaluate the success of the inactivation effect during treatment. These results indicate that nanocapsule-based photo treatment can be an alternative antibacterial strategy without contributing to antibiotic resistance, and thus can be used for both environmental and therapeutic applications.

Automated summary

This study introduces a new approach using gold nanocapsules for photothermal therapy against multidrug-resistant Staphylococcus aureus. The nanocapsules disrupt bacterial cell wall and membrane through photothermal action, prevent biofilm formation, and target multiple drug-resistant bacteria effectively. The photothermal effect combined with reactive oxygen species generation and loss of transmembrane potential contributes to successful bacterial inactivation within 30 minutes, without any observed development of resistance.