Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 32, Issue 51, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202209185
Keywords
amyloid fiber; biofilms; boron ester bindings; dispersant; drug deliveries; micelles; sepsis
Categories
Funding
- National Natural Science Foundation of China [51933006]
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pH-responsive micelles loaded with EGCG and ciprofloxacin can disperse biofilm bacteria and enhance bacterial killing by the immune system, providing a potential solution to antibiotic-resistant infections.
Amyloid-fibers help to maintain the structure of infectious biofilms. Disassembly of amyloid-fibers contributes to biofilm-dispersal in the blood-circulation, from which bacteria should be cleared by the host immune system. However, often the immune system is insufficiently prepared for increasing bacterial concentrations in blood, causing septic symptoms. Here, poly(ethylene glycol)/poly(beta-amino ester), pH-responsive micelles are prepared for co-delivery of (-)-epigallocatechin-3-O-gallate (EGCG) as a dispersant. Hydrophilic EGCG can not be loaded in the micellar core, but is cross-linked in the micellar shell through pH-reversible, boronic-ester binding. Disassembly of micelles under acidic biofilm conditions facilitates release of EGCG and dispersal of biofilm-bacteria. When core-loaded with ciprofloxacin, in-shell EGCG prevents ciprofloxacin-leakage at physiological pH. Bacterial killing by core-loaded ciprofloxacin in Staphylococcus aureus biofilms is enhanced when released in combination with EGCG in vitro and in vivo. In mice, micelles with in-shell EGCG self-target after tail-vein injection to an infection site, yielding dispersal of pathogens with mild septic symptoms and bacterial killing by the immune system. Septic symptoms disappear slightly faster when micelles are additionally core-loaded with ciprofloxacin. Thus, micelles with in-shell EGCG yield balanced biofilm dispersal inducing only mild septic symptoms, which is good news in an era of increasing antibiotic-resistance.
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