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Antibiotic-loaded polymersomes for clearance of intracellular burkholderia thailandensis

Antibiotic-loaded polymersomes for clearance of intracellular burkholderia thailandensis
Antibiotic-loaded polymersomes for clearance of intracellular burkholderia thailandensis

Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.

CARS imaging, Raman spectroscopy, antibiotics, imaging flow cytometry, intracellular bacteria, nanoparticles, polymersomes
1936-0851
19284-19297
Porges, Eleanor
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Jenner, Dominic
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Taylor, Adam W
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Harrison, James S P
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De Grazia, Antonio
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Hailes, Alethia R
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Wright, Kimberley M
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Whelan, Adam O
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Norville, Isobel H
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Prior, Joann L
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Mahajan, Sumeet
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Rowland, Caroline A
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Newman, Tracey A
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Evans, Nicholas D
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Porges, Eleanor
5a5e724b-0332-4b2a-a9a7-8e8085bc9ca4
Jenner, Dominic
a1941a7b-54e1-4e18-bb24-4235448c7bd3
Taylor, Adam W
85b7f242-2a82-4e68-bf8c-b976fc5848f6
Harrison, James S P
3bf4b4aa-9186-45bb-9888-87bf46284172
De Grazia, Antonio
ca329577-0e10-424e-a104-af068c935f07
Hailes, Alethia R
7b0cacd6-8fac-4898-a925-4818a35abea0
Wright, Kimberley M
930cc3e6-92e1-4692-8932-9cc70ea8fb47
Whelan, Adam O
9940e974-1d00-4ee8-b085-8d9de92e29d1
Norville, Isobel H
d6668803-6a93-4f4c-a5a2-97f487555569
Prior, Joann L
37a49e0c-a076-4c31-9508-c8d39764eb33
Mahajan, Sumeet
3e8fb3d0-f384-4182-ac26-b3063056a3c6
Rowland, Caroline A
61ff9bdd-665a-406d-90ef-bd84777f6103
Newman, Tracey A
322290cb-2e9c-445d-a047-00b1bea39a25
Evans, Nicholas D
06a05c97-bfed-4abb-9244-34ec9f4b4b95

Porges, Eleanor, Jenner, Dominic, Taylor, Adam W, Harrison, James S P, De Grazia, Antonio, Hailes, Alethia R, Wright, Kimberley M, Whelan, Adam O, Norville, Isobel H, Prior, Joann L, Mahajan, Sumeet, Rowland, Caroline A, Newman, Tracey A and Evans, Nicholas D (2021) Antibiotic-loaded polymersomes for clearance of intracellular burkholderia thailandensis. ACS Nano, 15 (12), 19284-19297. (doi:10.1021/acsnano.1c05309).

Record type: Article

Abstract

Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.

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Porges_et al_Pubmed central upload_incl_suppl_081121 - Accepted Manuscript
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Accepted/In Press date: 2021
e-pub ahead of print date: 5 November 2021
Published date: 28 December 2021
Additional Information: Funding Information: The authors acknowledge the kind financial support of the United Kingdom Ministry of Defence. N.D.E. acknowledges studentship support from the Institute for Life Sciences University of Southampton and the EPSRC (EP/K029150/1 and EP/M508147/1) for funding. S.M. acknowledges EP/N509747/1 and UKMoD for funding the studentship of J.S.P.H. S.M. also acknowledges funding from EPSRC grant EP/T020997/1. We acknowledge helpful advice from Prof. Peter Roach, University of Southampton. Funding Information: The authors acknowledge the kind financial support of the United Kingdom Ministry of Defence. N.D.E. acknowledges studentship support from the Institute for Life Sciences University of Southampton, and the EPSRC (EP/K029150/1 and EP/M508147/1) for funding. S.M. acknowledges EP/N509747/1 and UKMoD for funding the studentship of J.S.P.H. S.M. also acknowledges funding from EPSRC grant EP/T020997/1. We acknowledge helpful advice from Prof. Peter Roach, University of Southampton. Publisher Copyright: © 2021 American Chemical Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: CARS imaging, Raman spectroscopy, antibiotics, imaging flow cytometry, intracellular bacteria, nanoparticles, polymersomes
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Identifiers

Local EPrints ID: 452793
URI: http://eprints.soton.ac.uk/id/eprint/452793
DOI: doi:10.1021/acsnano.1c05309
ISSN: 1936-0851
PURE UUID: 918fdecb-a773-4f32-af20-a2a0a530b50c
ORCID for James S P Harrison: ORCID iD orcid.org/0000-0002-3643-0489
ORCID for Tracey A Newman: ORCID iD orcid.org/0000-0002-3727-9258
ORCID for Nicholas D Evans: ORCID iD orcid.org/0000-0002-3255-4388

Catalogue record

Date deposited: 20 Dec 2021 17:50
Last modified: 17 Mar 2024 06:56

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Contributors

Author: Eleanor Porges
Author: Dominic Jenner
Author: Adam W Taylor
Author: James S P Harrison ORCID iD
Author: Antonio De Grazia
Author: Alethia R Hailes
Author: Kimberley M Wright
Author: Adam O Whelan
Author: Isobel H Norville
Author: Joann L Prior
Author: Sumeet Mahajan
Author: Caroline A Rowland
Author: Tracey A Newman ORCID iD
Author: Nicholas D Evans ORCID iD

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