journal article·2021-12-28Open access

Antibiotic-Loaded Polymersomes for Clearance of Intracellular Burkholderia thailandensis

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

ACS Nano· Volume 15· Issue 12

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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Research context

OpenAlex topics: Burkholderia infections and melioidosis

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Affiliations

Bioengineering Sciences Group, Faculty of Engineering and the Environment, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom

Centre for Human Development, Stem Cells and Regeneration, Bone and Joint Research Group, University of Southampton Faculty of Medicine, Southampton SO16 6YD,United Kingdom

Clinical and Experimental Sciences, Faculty of Medicine, Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom

Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom

Chemical, Biological, and Radiological Division, Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, United Kingdom

London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom

School of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom

Funding

Engineering and Physical Sciences Research Council · University of Southampton · Ministry of Defence

References (67)

Show source-provided references
1. 10.1093/bmb/ldr00710.1093/bmb/ldr007 ↗
2. 10.1038/nmicrobiol.2015.810.1038/nmicrobiol.2015.8 ↗
3. 10.1016/j.vaccine.2017.03.02210.1016/j.vaccine.2017.03.022 ↗
4. Gilad J. · Isr. Med. Assoc. J. · 2007 · 9 · 499
5. 10.1016/j.mib.2015.11.00710.1016/j.mib.2015.11.007 ↗
6. 10.1371/journal.ppat.100520810.1371/journal.ppat.1005208 ↗
7. 10.1128/CMR.18.2.383-416.200510.1128/CMR.18.2.383-416.2005 ↗
8. 10.1128/IAI.68.9.5377-5384.200010.1128/IAI.68.9.5377-5384.2000 ↗
9. 10.1086/51385010.1086/513850 ↗
10. 10.1155/2015/47653410.1155/2015/476534 ↗
11. 10.1016/S0966-842X(00)01854-010.1016/S0966-842X(00)01854-0 ↗
12. 10.7205/MILMED-D-03-080810.7205/MILMED-D-03-0808 ↗
13. 10.1016/S0035-9203(00)90333-X10.1016/S0035-9203(00)90333-X ↗
14. 10.1073/pnas.100008710710.1073/pnas.1000087107 ↗
15. 10.7759/cureus.140310.7759/cureus.1403 ↗
16. 10.1126/science.284.5417.114310.1126/science.284.5417.1143 ↗
17. 10.1016/j.nano.2018.02.01410.1016/j.nano.2018.02.014 ↗
18. 10.1039/c3nr03250g10.1039/c3nr03250g ↗
19. 10.1016/j.addr.2012.09.03710.1016/j.addr.2012.09.037 ↗
20. 10.1128/AAC.32.8.120410.1128/AAC.32.8.1204 ↗
21. 10.1093/jac/33.3.50910.1093/jac/33.3.509 ↗
22. 10.1016/j.ajps.2014.08.01010.1016/j.ajps.2014.08.010 ↗
23. 10.1016/j.jconrel.2010.06.00210.1016/j.jconrel.2010.06.002 ↗
24. 10.1021/ja056514l10.1021/ja056514l ↗
25. 10.1002/adma.20070094110.1002/adma.200700941 ↗
26. 10.1039/c1sm05880k10.1039/c1sm05880k ↗
27. 10.1021/bm070085x10.1021/bm070085x ↗
28. 10.1021/ja110275f10.1021/ja110275f ↗
29. 10.1016/S1369-7021(12)70195-510.1016/S1369-7021(12)70195-5 ↗
30. 10.1016/j.jconrel.2010.07.12310.1016/j.jconrel.2010.07.123 ↗
31. 10.1002/btm2.1014310.1002/btm2.10143 ↗
32. 10.1096/fj.12-22521910.1096/fj.12-225219 ↗
33. 10.1016/j.colsurfb.2015.10.04910.1016/j.colsurfb.2015.10.049 ↗
34. 10.1021/acs.biomac.9b0021410.1021/acs.biomac.9b00214 ↗
35. 10.1016/j.jconrel.2020.02.02610.1016/j.jconrel.2020.02.026 ↗
36. 10.1021/acsnano.0c0187010.1021/acsnano.0c01870 ↗
37. 10.1039/C4PY01249F10.1039/C4PY01249F ↗
38. 10.1002/cyto.a.2280910.1002/cyto.a.22809 ↗
39. 10.1039/C8IB00050F10.1039/C8IB00050F ↗
40. 10.1038/srep2946010.1038/srep29460 ↗
41. 10.1016/S0140-6736(03)13374-010.1016/S0140-6736(03)13374-0 ↗
42. 10.3389/fcimb.2018.0021010.3389/fcimb.2018.00210 ↗
43. 10.1016/j.ejpb.2008.01.02510.1016/j.ejpb.2008.01.025 ↗
44. 10.1021/acsnano.0c0187010.1021/acsnano.0c01870 ↗
45. 10.1016/j.jconrel.2004.10.01410.1016/j.jconrel.2004.10.014 ↗
46. 10.1002/jrs.317010.1002/jrs.3170 ↗
47. 10.1021/jp073478z10.1021/jp073478z ↗
48. 10.3109/17435390.2014.99248710.3109/17435390.2014.992487 ↗
49. 10.1021/mp800137z10.1021/mp800137z ↗
50. 10.1016/j.jconrel.2013.11.00210.1016/j.jconrel.2013.11.002 ↗
51. 10.1002/jbio.20130011010.1002/jbio.201300110 ↗
52. 10.1128/AAC.06049-1110.1128/AAC.06049-11 ↗
53. 10.1242/jcs.12181410.1242/jcs.121814 ↗
54. 10.1016/j.ijpharm.2007.05.06210.1016/j.ijpharm.2007.05.062 ↗
55. 10.1128/AAC.05993-1110.1128/AAC.05993-11 ↗
56. 10.1038/srep2626910.1038/srep26269 ↗
57. 10.1186/s11671-018-2728-610.1186/s11671-018-2728-6 ↗
58. 10.1091/mbc.E17-06-041910.1091/mbc.E17-06-0419 ↗
59. 10.3389/fmicb.2011.0017010.3389/fmicb.2011.00170 ↗
60. 10.1023/A:101898530898410.1023/A:1018985308984 ↗
61. 10.7150/ntno.3708010.7150/ntno.37080 ↗
62. 10.1002/jbm.82019040810.1002/jbm.820190408 ↗
63. Arakawa C. K. · 2017 · 29510.1016/B978-0-12-802734-9.00019-6 ↗
64. 10.1038/srep2946010.1038/srep29460 ↗
65. 10.1016/j.polymdegradstab.2009.12.00510.1016/j.polymdegradstab.2009.12.005 ↗
66. 10.1186/1475-925X-2-1310.1186/1475-925X-2-13 ↗
67. 10.1038/nmeth.207510.1038/nmeth.2075 ↗