Gold nanocluster based nanocomposites for combinatorial antibacterial therapy for eradicating biofilm forming pathogens

Abstract

Nanomaterial-based antimicrobial photodynamic therapy (aPDT) is a promising approach for the eradication of drug-resistant bacterial biofilms. However, the intrinsic cytotoxicity of commonly used nanomaterials and their limited capacity to generate reactive oxygen species (ROS) have remained major shortcomings for their use in aPDT. In this study, we report a nanocomposite design strategy that integrates a non-toxic, well-defined antimicrobial gold nanocluster protected with mercaptopropionic acid (denoted Au₁₈(MPA)₁₄ NC), and a photosensitizer, protoporphyrin (PpIX), within a chitosan polymer matrix (the nanocomposite is denoted as PpIX–Chito–Au₁₈). The nanocomposite showed ∼2 times higher ROS generation capacity upon white light irradiation and thus effectively killed both Gram-positive and Gram-negative pathogens by damaging their membrane and DNA. Furthermore, our confocal laser scanning microscopy (CLSM) data demonstrated that the PpIX–Chito–Au₁₈ nanocomposite (white light irradiated) has better biofilm penetration and elimination capacity (against both S. aureus and P. aeruginosa biofilms) than Au₁₈(MPA)₁₄ NCs alone or the nanocomposite (under dark conditions), revealing the efficacy of the combinatorial therapy through a synergistic killing mechanism. Our work deepens the understanding of the importance of combinatorial antimicrobial therapy using metal NCs and offers the opportunity to explore them in various areas where drug-resistant pathogens are concerned.