Human leukocyte elastase triggered nanoparticles for targeted antimicrobial delivery and oral microbial modulation

Hadis, MA, Insua, I, Raja, FNS, Alvara, VG, Palin, WM, Milward, MR, Cooper, PR, Kuehne, SA ORCID: https://orcid.org/0000-0001-6790-8433, Addison, O and Fernandez-Trillo, P, 2026. Human leukocyte elastase triggered nanoparticles for targeted antimicrobial delivery and oral microbial modulation. Advanced NanoBiomed Research. ISSN 2699-9307 (Forthcoming)

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Abstract

This study investigated targeted antimicrobial delivery through enzyme-responsive polyelectrolyte complex (PIC) nanoparticles of peptides and antimicrobials. Nanoparticles released chlorhexidine upon enzymatic activation by human leukocyte elastase (HLE), mimicking conditions present at inflamed or infected sites, and utilized as a semi-specific trigger for oral disease. Peptides P1-P4 and P6-P8 were tailored with HLE cleavable sequence alanine-alanine-proline-valine (AAPV) and flanked with cysteine and glutamic acid residues to enhance solubility, disulfide oxidation, and HLE sensitivity and specificity. Dynamic light scattering confirmed particle formation across various antimicrobial biguanide and peptide carboxylate ratios (N:COOH), with optimal size distribution and autocorrelation profiles observed for P7 (ECAAPVCE; N:COOH of 1:0.3). P7-chlorhexidine based nanoparticles demonstrated structural stability in physiological conditions. Nanoparticle treatment of commensal Streptococcus sanguinis, and pathogenic Streptococcus mutans and Porphyromonas gingivalis delayed bacterial growth in a time-, concentration-, and HLE-dependent manner (p<0.05). Subinhibitory effects without HLE suggested residual chlorhexidine was below the minimum inhibitory concentration, while the presence of HLE enhanced antimicrobial effects, leading to complete inhibition of pathogenic species and transient growth inhibition of commensal species. These findings support development of HLE-responsive nanoparticle systems for targeted antimicrobial delivery, with potential for modulating microbial communities and providing site-specific therapy in oral and other inflammatory infections.

Item Type:	Journal article
Publication Title:	Advanced NanoBiomed Research
Creators:	Hadis, M.A., Insua, I., Raja, F.N.S., Alvara, V.G., Palin, W.M., Milward, M.R., Cooper, P.R., Kuehne, S.A., Addison, O. and Fernandez-Trillo, P.
Publisher:	Wiley
Date:	19 March 2026
ISSN:	2699-9307
Identifiers:	Number Type 2598396 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	13 Apr 2026 08:35
Last Modified:	13 Apr 2026 08:35
URI:	https://irep.ntu.ac.uk/id/eprint/55535

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