Antimicrobial Photodynamic Therapy with Ga-Protoporphyrin Derivatives Against Pathogenic Bacteria
Abstract: Bacterial pathogens have the ability to acquire hemin through different mechanisms. One mechanism is through cell-surface hemin receptors (CSHRs), which are capable of rapid hemin recognition and make the bacteria vulnerable to antimicrobial photodynamic inactivation (aPDI). The work presented here focuses on gallium protoporphyrin IX (GaPpIX) as a photosensitizer for aPDI against staphylococci. GaPpIX is rapidly uptaken into CSHR-expressing bacteria, and is easily detected within minutes of exposure. Assessment of GaPpIX as a photosensitizer against laboratory strains of Staphylococcus aureus, clinical isolates of methicillin-resistant S. aureus (MRSA), and S. epidermis shows aPDI activity at low micromolar levels, following 15 minutes of exposure to a compact fluorescent light bulb or at nanomolar levels when exposed for 10 seconds with a light-emitting diode light source. Activity also had greater potency when compared against metal-free protoporphyrin (PpIX). These results led to the design of a more potent photosensitizer by incorporating GaPpIX into apohemoglobin (GaPpIXHb) and using the hybrid protein to coat 10-nm silver nanoparticles (AgNPs). The GaPpIXHb-AgNP complexes exhibit remarkable aPDI activity using nanomolar loadings of GaPpIX against clinical MRSA isolates.