One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model

Akhilesh Rai, Sandra Pinto, Tiago R Velho, André F Ferreira, Catarina Moita, Urvish Trivedi, Marta Evangelista, Michela Comune, Kendra P. Rumbaugh, Pedro N Simões, Luís Moita, Lino Ferreira

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

143 Citationer (Scopus)

Abstract

The increase in antibiotic drug resistance and the low number of new antibacterial drugs approved in the last few decades requires the development of new antimicrobial strategies. Antimicrobial peptides (AMPs) are very promising molecules to fight microbial infection since they kill quickly bacteria and, in some cases, target bacterial membrane. Although some AMPs may be stable against proteolytic degradation by chemical modification, in general, low AMP activity and stability in the presence of serum and proteolytic enzymes as well as their cytotoxicity have impaired their clinical translation. Here, we describe a one-step methodology to generate AMP-conjugated gold nanoparticles (Au NPs), with a high concentration of AMPs (CM-SH) (≈240 AMPs per NP), controlled size (14 nm) and low polydispersity. AMP-conjugated Au NPs demonstrated higher antimicrobial activity and stability in serum and in the presence of non-physiological concentrations of proteolytic enzymes than soluble AMP, as well as low cytotoxicity against human cells. Moreover, the NPs demonstrated high antimicrobial activity after in vivo administration in a chronic wound and in an animal model of systemic infection.

OriginalsprogEngelsk
TidsskriftBiomaterials
Vol/bind85
Sider (fra-til)99-110
Antal sider12
ISSN0142-9612
DOI
StatusUdgivet - 2016
Udgivet eksterntJa

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Copyright © 2016 Elsevier Ltd. All rights reserved.

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