Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis Management
Open accessAbstract
Sepsis is a life‐threatening disease resulted from a dysregulated host immune response to bacterial infections, continuing to cause high morbidity and mortality worldwide. Despite discoveries of many potential therapeutic targets, effective treatments of sepsis are lacking. Here, a strategy is reported to target infectious microenvironments (IMEs) via bioresponsive nanoparticles that simultaneously eliminate bacteria and alleviate the host inflammation response, thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to pH and bacterial enzymes to self‐assemble into a micelle loaded with both an antibiotic (ciprofloxacin) and an anti‐inflammatory agent ((2‐[(aminocarbonyl)amino]‐5‐(4‐fluorophenyl)‐3‐thiophenecarboxamide). In addition, the nanoparticle is conjugated with intercellular adhesion molecule‐1 antibodies to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to deliver therapeutics in on‐demand manners is demonstrated using an acute lung bacterial infection mouse model. In the sepsis mouse model induced by peritonitis at a lethal dose of bacterial invasion, it is shown that concurrently targeting pathogens and excessive inflammation pathways is valuable to manage the sepsis. The study illustrates not only the development of a new delivery system but also the mechanism‐based therapy of nanomedicine for infectious diseases.
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In a mouse model of pulmonary P. aeruginosa infection, treatment with targeted nanoparticles improved survival over the free-drug control by nearly 50 percentage points.
“In a mouse model of pulmonary P. aeruginosa infection, treatment with targeted nanoparticles improved survival over the free-drug control by nearly 50 percentage points.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [62]
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- Authors
- Zhang, C. Y., Gao, J., & Wang, Z.
- Affiliations
- Washington State University Spokane (US)
- Corresponding author
- Wang, Zhenjia
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2018-09-11
- Volume
- 30
- Issue
- 43
- Pages
- e1803618-e1803618
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- PMC
- PMC6197919
- OpenAlex
- W2890443562
- Cited by
- 222
- References
- 59
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 32 · 2023: 40 · 2022: 32 · 2021: 34 · 2020: 25 · 2019: 21 · 2018: 2
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (RO1GM116823)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- sepsis, pH-responsive polymers, enzyme-responsive polymers, micelles, ciprofloxacin, anti-inflammatory agents, targeted drug delivery, bacterial infection, peritonitis, pulmonary infection, inflammation, nanomedicine
- MeSH terms
- Proof of Concept Study, Amides, Animals, Anti-Inflammatory Agents, Non-Steroidal, Anti-Bacterial Agents, Bacterial Proteins, Ciprofloxacin, Disease Models, Animal, Humans, Hydrogen-Ion Concentration, Lung Diseases, Micelles, Peritonitis, Polymers, Thiophenes, Drug Design, Drug Delivery Systems, Sepsis, Mice, Nanoparticles, Human Umbilical Vein Endothelial Cells
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