Format

Send to

Choose Destination
Int J Hyperthermia. 2018 Mar;34(2):209-219. doi: 10.1080/02656736.2017.1392047.

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

Author information

1
a Department of Microbiology and Immunology , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
2
b Department of Chemistry and Biochemistry , University of Arkansas , Fayetteville , AR , USA.
3
c Phillips Classic Laser and Nanomedicine Laboratories , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
4
d Department of Radiation Oncology , University of Arkansas for Medical Sciences , Little Rock , AR , USA.
5
e Department of Microbial Pathogenesis , Dental School, University of Maryland-Baltimore , Baltimore , MD , USA.
6
f Department of Microbiology and Immunology , School of Medicine, University of Maryland-Baltimore , Baltimore , MD , USA.

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.

CONCLUSIONS:

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.

KEYWORDS:

Photothermal killing; Pseudomonas aeruginosa; Staphylococcus aureus; biofilms; gold nanocages

PMID:
29025325
PMCID:
PMC6095133
DOI:
10.1080/02656736.2017.1392047
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center