Bacterial Toxin-Triggered Drug Release from Gold Nanoparticle-Stabilized Liposomes for the Treatment of Bacterial Infection

Abstract

We report a new approach to selectively delivering antimicrobials to the sites of bacterial infections by utilizing bacterial toxins to activate drug release from gold nanoparticle-stabilized phospholipid liposomes. The binding of chitosan modified gold nanoparticles to the surface of liposomes can effectively prevent them from fusing with one another and from undesirable payload release in regular storage or physiological environments. However, once these protected liposomes "see" bacteria that secrete toxins, the toxins will insert into the liposome membranes and form pores, through which the encapsulated therapeutic agents are released. The released drugs subsequently impose antimicrobial effects on the toxin-secreting bacteria. Using methicillinresistant Staphycoccus aureus (MRSA) as a model bacterium and vacomycin as a model anti-MRSA antibiotic, we demonstrate that the synthesized gold nanoparticle-stabilized liposomes can completely release the encapsulated vacomycin within 24 h in the presence of MRSA bacteria and lead to inhibition of MRSA growth as effective as an equal amount of vacomycin loaded liposomes (without nanoparticle stabilizers) and free vacomycin. This bacterial toxin enabled drug release from nanoparticle-stabilized liposomes provides a new, safe and effective approach for the treatment of bacterial infections. This technique can be broadly applied to treat a variety of infections caused by bacteria that secrete pore-forming toxins.

Nanomaterials for alternative antibacterial therapy

“…142 Lipids like phosphatidylinositol and stearylamine presented specific affinity with biofilms, thereby increasing the biofilm adhesion of liposomes. Anti-biofilm activities of phosphatidylcholine-decorated Au NPs loaded with gentamycin have been reported against P. aeruginosa, S. aureus as well as intracellular Listeria monocytogenes and E. coli.…”

Sustained Broad-Spectrum Antibacterial Effects of Nanoliposomes Loaded with Silver Nanoparticles

“…However, the use of liposomes as a delivery system is limited by their instability. Among the attempts used to stabilize liposomes, one is coating their surface with polymers, but this has impeded drug release and interfered with liposomal ability to fuse with bacterial membranes [16][17][18]. More recently, bacterial toxins were used to activate drug release from gold nanoparticle-stabilized liposomes [18].…”

Review: the potential impact of surface crystalline states of titanium for biomedical applications

“…In this context, many studies have been performed to limit bacterial adhesion to address early infection (Glinel et al, 2012, Emmerson, 1998, Harris et al, 2004, Klok and Genzer, 2015, Eckhardt et al, 2013, Qiao et al, 2015. In addition, another solution is the bactericidal surfaces that can kill bacteria once in the contact with the implant surface (Popat et al, 2007, Özçelik et al, 2015, Pornpattananangkul et al, 2011.…”