Surface-Adaptive Gold Nanoparticles with Effective Adherence and Enhanced Photothermal Ablation of Methicillin-Resistant <i>Staphylococcus aureus</i> Biofilm

TLDR

Biofilms cause persistent infections and resist antibiotics and immune attacks, posing a serious public health threat. The study develops surface‑adaptive gold nanoparticles that target acidic biofilms, enhance near‑infrared photothermal killing of MRSA biofilm, and spare surrounding healthy tissue. AuNPs were prepared by coating with pH‑responsive mixed‑charged zwitterionic monolayers of 11‑mercaptoundecanoic acid and 10‑mercaptodecyltrimethylammonium bromide, enabling a rapid charge switch from negative at neutral pH to positive at acidic pH, which promotes dispersion in healthy tissues and strong adhesion to MRSA biofilm surfaces. In MRSA biofilm, AuNP aggregation amplified NIR photothermal ablation, while in healthy tissues the dispersed particles showed no photothermal effect, indicating effective biofilm eradication without collateral damage and potential for clinical antibacterial use.

Abstract

Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.