Fenaroli, F., Robertson, J.D., Scarpa, E. et al. (16 more authors) (2020) Polymersomes eradicating intracellular bacteria. ACS Nano, 14 (7). pp. 8287-8298. ISSN 1936-0851
Abstract
Mononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world’s population infected and an average of 1.8 million deaths/year worldwide. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to infected macrophages both in vitro and in vivo, using pH-sensitive nanoscopic polymersomes made of PMPC–PDPA block copolymer. Polymersomes showed the ability to significantly enhance the efficacy of the antibiotics killing Mycobacterium bovis, Mycobacterium tuberculosis, and another established intracellular pathogen, Staphylococcus aureus. Moreover, they demonstrated to easily access TB-like granuloma tissues—one of the harshest environments to penetrate—in zebrafish models. We thus successfully exploited this targeting for the effective eradication of several intracellular bacteria, including M. tuberculosis, the etiological agent of human TB.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 American Chemical Society. This is an author-produced version of a paper subsequently published in ACS Nano. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | polymersomes; intracellular pathogens; tuberculosis; zebrafish; drug delivery |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 105570/Z/14/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Jun 2020 09:20 |
Last Modified: | 03 Nov 2021 17:46 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acsnano.0c01870 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:162384 |