Dual-functional gold nanoparticles with antimicrobial and proangiogenic activities improve the healing of multidrug-resistant bacteria-infected wounds in diabetic mice

Abstract

Gold nanoparticles (Au NPs) are conjugated with the vascular endothelial growth factor-A(165) (VEGF-A(165)) and (11-mercaptoundecyl)-N,N,N-trimethylammonium (11-MTA) cation to form dual-functional gold nanoparticles (11-MTA/VEGF-Au NPs) that possess antimicrobial and proangiogenic activities for wound healing in diabetic (db/db) mice. VEGF-A(165) is a popular proangiogenic growth factor that stimulates multiple components in the wound-healing cascade. On the other hand, 11-MTA possesses antibacterial activity and can be bound to Au NPs easily through Au-S bonding. We have found that the surface density of VEGF-A(165) plays a vital role in promoting the proliferation, migration, and tube formation of human umbilical vein endothelial cells. 11-MTA tethered on the VEGF-modified Au NPs enables the nanocomposites (i.e., 11-MTA/VEGF-Au NPs) to exhibit a strong antimicrobial activity against multidrug-resistant bacteria [methicillin-resistant S. aureus (MRSA)]. The minimal inhibition concentration of 11-MTA/VEGF-Au NPs is similar to 450-fold lower than that of 11-MTA, revealing their high antibacterial efficiency. 11-MTA/VEGF-Au NPs exhibit high biocompatibility. 11-MTA/VEGF-Au NPs as dressing materials to treat MRSA-infected wounds in diabetic mice not only show strong in vivo bactericidal activities but also enhance the healing process of the formation of collagen fibers and epithelialization. Our results show that dual-functional 11-MTA/VEGF-Au NPs are promising agents for clinical applications like treating chronic wound infections.