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Pursuing intracellular pathogens with hyaluronan. From a 'pro-infection' polymer to a biomaterial for 'trojan horse' systems

Montanari, Elita; Di Meo, Chiara; Oates, Angela; Coviello, Tommasina; Matricardi, Pietro


Elita Montanari

Chiara Di Meo

Tommasina Coviello

Pietro Matricardi


© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is 'Cluster of Differentiation 44' (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as 'reservoirs' for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a 'Trojan Horse'. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials.


Montanari, E., Di Meo, C., Oates, A., Coviello, T., & Matricardi, P. (2018). Pursuing intracellular pathogens with hyaluronan. From a 'pro-infection' polymer to a biomaterial for 'trojan horse' systems. Molecules, 23(4), 939.

Journal Article Type Article
Acceptance Date Apr 13, 2018
Online Publication Date Apr 18, 2018
Publication Date Apr 18, 2018
Deposit Date Jan 16, 2019
Publicly Available Date Oct 27, 2022
Journal Molecules
Electronic ISSN 1420-3049
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 23
Issue 4
Pages 939
Keywords Hyaluronan; Intracellular infections; CD44; Nano-carriers; Antimicrobial delivery
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Copyright Statement
©2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (

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