Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 33, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202202559
Keywords
Biofilms; Drug Design; Heterogeneity; Pharmacokinetic Complementarity; Yolk-Shell Nanoplatform
Categories
Funding
- New Direction Award of Institute of Process Equipment [109200 542810/067/005]
- Fundamental Research Funds for the Central Universities [109209*17221012001, 2 2050205 20 489]
- National Natural Science Foundation of China [22177114]
- Chinese Academy of Sciences [YJKYYQ20210010]
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Heterogeneity in biofilms is a major challenge in biofilm therapies. This study presents a therapeutic strategy that overcomes biofilm heterogeneity by separately loading an antibacterial agent and an EPS dispersant in different compartments of a yolk-shell nanoplatform. The strategy takes advantage of the pharmacokinetic complementarity of ROS and NO to penetrate the biofilm and eliminate bacteria.
The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)-inducing Fe3+) were separately loaded in the yolk and shell compartment of a yolk-shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three-dimensional spherical biofilm model is novel and clinically relevant.
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