Versatility of targeted antibiotic-loaded gold nanoconstructs for the treatment of biofilm-associated bacterial infections

Abstract

Background. We previously demonstrated that a photoactivatable therapeutic approach employing antibiotic-loaded, antibody-conjugated, polydopamine (PDA)-coated gold nanocages (AuNCs) could be used for the synergistic killing of bacterial cells within a biofilm. The approach was validated with a focus on Staphylococcus aureus using an antibody specific for staphylococcal protein A (Spa) and an antibiotic (daptomycin) active against Gram-positive cocci including methicillin-resistant S. aureus (MRSA). However, an important aspect of this approach is its potential therapeutic versatility. Methods. In this report, we evaluated this versatility by examining the efficacy of AuNC formulations generated with alternative antibodies and antibiotics targeting S. aureus and alternative combinations targeting the Gram-negative pathogen Pseudomonas aeruginosa. Results. The results confirmed that daptomycin-loaded AuNCs conjugated to antibodies targeting two different S. aureus lipoproteins (SACOL0486 and SACOL0688) also effectively kill MRSA in the context of a biofilm. However, our results also demonstrate that antibiotic choice is critical. Specifically, ceftaroline and vancomycin-loaded AuNCs conjugated to anti-Spa antibodies were found to exhibit reduced efficacy relative to daptomycin-loaded AuNCs conjugated to the same antibody. In contrast, gentamicin-loaded AuNCs conjugated to an antibody targeting a conserved outer membrane protein were highly effective against P. aeruginosa biofilms. Conclusion. These results confirm the therapeutic versatility of our approach. However, to the extent that its synergistic efficacy is dependent on the ability to achieve both a lethal photothermal effect and the thermally-controlled release of a sufficient amount of antibiotic, they also demonstrate the importance of carefully designing appropriate antibody and antibiotic combinations to achieve the desired therapeutic synergy.

Advances in Hollow Inorganic Nanomedicines for Photothermal-Based Therapies

“…In 2018, the authors developed PDA-coated AuNCs with various antibodies and antibiotics to evaluate the versatility of their previous method. 101 In this study, the authors successfully verified the versatility of the method by inhibiting the growth of the gram-negative pathogen Pseudomonas aeruginosa using a novel combination of antibiotics and antibodies. Further, to tackle the problem of MDR, Zhou et al fabricated gold-silver nanoshells (AuAgNSs) for wound healing.…”

Antibody-Functionalized MoS2 Nanosheets for Targeted Photothermal Therapy of Staphylococcus aureus Focal Infection

“…Protein A is a surface protein in the cell wall of S. aureus . Anti-protein A IgG has proven effective to target S. aureus , and used here as the targeting moiety (Meeker et al, 2016, 2018).…”

“…Thus, PTT possesses great potential for the treatment of bacterial biofilm-related infections. Many nanomaterials have been used as PTT agents for the photothermal destruction of bacterial biofilms, such as various gold-based nanostructures and carbon nanomaterials (Jo and Kim, 2013; Levi-Polyachenko et al, 2014; Pallavicini et al, 2014; Ji et al, 2016; Meeker et al, 2016, 2018; Teng et al, 2016; Hu et al, 2017). However, relatively high temperature is usually needed to eliminate bacterial biofilms completely by PTT, which would cause harm to surrounding healthy tissues and limit the application of PTT (Hauck et al, 2008; Hsiao et al, 2015).…”

Prospects for the Use of New Technologies to Combat Multidrug-Resistant Bacteria

“…They can be synthesized from various substances, including metals, proteins, and polymers, and have been investigated in terms of their potential for combating multidrug-resistant bacteria. Reported advantages of these structures are that they provide greater adhesion, retention at the site of infection, increased systemic circulation, and good biocompatibility (Wang et al, 2016; Mekeer et al, 2018).…”