Ultrasound-responsive nanoparticles enable hydrophobic antibiotic release and deep penetration for biofilm treatment

Odyniec, ML, Bell, DJ, Gallant, BM, Firdaus, R, Ball, G, Hughes, L, Oxtoby, R, Hewitt, BJ, Williams, CM, Muguruza, AR, Overton, TW, Tsai, H-J, Chiu, Y-L, Kubicki, DJ, Walmsley, AD, Kuehne, SA ORCID: https://orcid.org/0000-0001-6790-8433 and Pikramenou, Z, 2026. Ultrasound-responsive nanoparticles enable hydrophobic antibiotic release and deep penetration for biofilm treatment. JACS Au. ISSN 2691-3704 (Forthcoming)

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Abstract

Localised delivery of antibiotics is a promising strategy to lead to transformative treatment pathways of bacterial biofilms and increase the effectiveness of their administration in contrast to traditional delivery methods requiring high antibiotic doses. Hydrophobic antibiotics have poor activity against bacterial biofilms due to their limited penetration and are particularly challenging to deliver. Nanoparticles are ideal drug delivery agents to achieve spatially controlled delivery but commonly their designs are either soft or porous which limit temporally triggered release with the result that most of the antibiotic does not reach deeply into the biofilm. In this study, we present designs of non-porous silica nanoparticles that encapsulate a lipophilic antibiotic, rifampicin, with non-covalent interactions and enable controlled release triggered by Low Frequency Ultrasound (LFUS). Staphylococcus aureus biofilms treated with the non-porous, core@shell, rifampicin encapsulated nanoparticles, RIF⊂PhSiO2@SiO2 combined with LFUS achieved 90 % biofilm eradication, compared to 20 % without ultrasound; treatment with free rifampicin and LFUS resulted only in a 10 % reduction. Nanoparticle penetration into biofilm layers, was visualised using fluorescent nanoparticles prepared with co-encapsulation of Nile red fluorophore, RIF+NR⊂PhSiO2@SiO2, Confocal fluorescence imaging of the biofilms demonstrated penetration of the nanoparticles throughout all the layers of the biofilm upon LFUS application, in sharp contrast to their presence in only the top few biofilm layers without LFUS. Scanning Electron Microscopy of the biofilms confirmed the presence of nanoparticles and the dual role of LFUS in promoting penetration and facilitating drug release by disrupting molecular interactions within the nanoparticle. This work introduces a design paradigm for non-porous nanoparticle agents combined with ultrasound, enabling both temporal and spatial control of drug release in bacterial biofilms. This will open transformative therapeutic approaches for effective localised delivery of drugs that have previously been challenging to deliver.

Item Type:	Journal article
Publication Title:	JACS Au
Creators:	Odyniec, M.L., Bell, D.J., Gallant, B.M., Firdaus, R., Ball, G., Hughes, L., Oxtoby, R., Hewitt, B.J., Williams, C.M., Muguruza, A.R., Overton, T.W., Tsai, H.-J., Chiu, Y.-L., Kubicki, D.J., Walmsley, A.D., Kuehne, S.A. and Pikramenou, Z.
Publisher:	American Chemical Society
Date:	19 February 2026
ISSN:	2691-3704
Identifiers:	Number Type 2581203 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	25 Feb 2026 09:26
Last Modified:	25 Feb 2026 09:26
URI:	https://irep.ntu.ac.uk/id/eprint/55330

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