Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis

Author:

Lin Chin‐Jung1,Hwang Tsong‐Long2345,Wang Robert Y. L.6,Nain Amit7,Shih Ren‐Hong8,Chang Lung910,Lin Han‐Jia811,Harroun Scott G.12,Chang Huan‐Tsung131415,Huang Chih‐Ching81116ORCID

Affiliation:

1. Institute of Analytical and Environmental Sciences, National Tsing Hua University Hsinchu 30013 Taiwan

2. Graduate Institute of Biomedical Sciences Graduate Institute of Natural Products College of Medicine Chang Gung University Taoyuan 33302 Taiwan

3. Research Center for Chinese Herbal Medicine Graduate Institute of Healthy Industry Technology College of Human Ecology Chang Gung University of Science and Technology Taoyuan 33302 Taiwan

4. Department of Anesthesiology Chang Gung Memorial Hospital Taoyuan 33302 Taiwan

5. Department of Chemical Engineering Ming Chi University of Technology New Taipei City 243303 Taiwan

6. Division of Microbiology and Immunology Graduate Institute of Biomedical Sciences College of Medicine Chang Gung University Taoyuan 33302 Taiwan

7. Department of Materials Engineering Indian Institute of Science Bengaluru Karnataka 520012 India

8. Department of Bioscience and Biotechnology National Taiwan Ocean University Keelung 202301 Taiwan

9. Department of Pediatrics Mackay Memorial Hospital and Mackay Junior College of Medicine Nursing and Management Taipei 10449 Taiwan

10. Department of Medicine MacKay Medical College New Taipei City 25245 Taiwan

11. Center of Excellence for the Oceans National Taiwan Ocean University Keelung 20231 Taiwan

12. Department of Engineering Physics Polytechnique Montréal, Montréal Québec H3T 1J4 Canada

13. Graduate Institute of Biomedical Sciences Chang Gung University Taoyuan 33302 Taiwan

14. Center for Advanced Biomaterials and Technology Innovation Chang Gung University Taoyuan 33302 Taiwan

15. Division of Breast Surgery Department of General Surgery Chang‐Gung Memorial Hospital, Linkou Taoyuan 33305 Taiwan

16. School of Pharmacy College of Pharmacy Kaohsiung Medical University Kaohsiung 80708 Taiwan

Abstract

AbstractSepsis is a life‐threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin‐resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as‐formed CCM‐CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM‐CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA‐induced septic mouse model, it is observed that CCM‐CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti‐inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM‐CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM‐CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA‐infected mice treated with CCM‐CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life‐threatening infectious diseases.

Funder

National Science and Technology Council

Publisher

Wiley

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