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Title: Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential
Authors: Comune, Michela 
Rai, Akhilesh 
Chereddy, Kiran K
Pinto, Sandra
Aday, Sezin
Ferreira, André F
Zonari, Alessandra
Blersch, Josephine
Cunha, Rodrigo Pinto Antunes da 
Rodrigues, Ricardo
Lerma, Juan 
Simões, Pedro Nuno 
Préat, Veronique
Ferreira, Lino 
Keywords: Antimicrobial peptide; EGFR transactivation; Keratinocytes; LL37; P2X7 receptor; Purinergic receptors; Wound healing
Issue Date: 28-Sep-2017
Publisher: Elsevier
Project: The authors would like to thank the financial support of EC (ERC project nº 307384, “Nanotrigger”; Marie Curie ITN “NANODRUG”, FP7-PEOPLE-2011-ITN). The work was also funded by COMPETE in the context of the project “Stem cell based platforms for Regenerative and Therapeutic Medicine” (Centro-07-ST24-FEDER-002008). 
Volume: 262
Abstract: Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process. The antimicrobial peptide (AMP) LL37 combines antimicrobial with pro-regenerative properties and thus represents a promising topical therapy to address both problems. Here, we investigated the wound healing potential of soluble and immobilized LL37 (LL37-conjugated gold nanoparticles, LL37-Au NPs), both in vitro (migration of keratinocytes) and in vivo (skin wound healing). Our results show that LL37-Au NPs, but not LL37 peptide, have the capacity to prolong the phosphorylation of EGFR and ERK1/2 and enhance the migratory properties of keratinocytes in a large in vitro wound model. We further report that both LL37 and LL37-Au NPs promote keratinocyte migration by the transactivation of EGFR, a process that seems to be initiated at the P2X7 receptor, as confirmed by chemical and genetic inhibition studies. Finally, we show in vivo that LL37-Au NPs have higher wound healing activity than LL37 peptide in a splinted mouse full thickness excisional model. Animal wounds treated by LL37-Au NPs have higher expression of collagen, IL6 and VEGF than the ones treated with LL37 peptide or NPs without LL37. Altogether, the conjugation of AMPs to NPs offers a promising platform to enhance their pro-regenerative properties.
ISSN: 01683659
DOI: 10.1016/j.jconrel.2017.07.007
Rights: openAccess
Appears in Collections:UC Bibliotecas - Artigos em Revistas Internacionais

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