Honeybee-mimicking microenvironment-responsive theranostic nanovesicles for enhanced magnetic resonance imaging and targeted thrombolytic therapy
File(s)
Author(s)
Type
Journal Article
Abstract
Developing a theranostic system integrating specific thrombus targeting, microenvironment-responsive drug release and imaging remains challenging. Inspired by “honeybees finding nectars”, we first designed a honeybee-mimicking nanovesicle (denoted as tPA@THPTN), which mimics honeybees' ability to seek (target), to respond (release drug in the target microenvironment), and to report (provide real-time location feedback) for targeted delivery of tissue plasminogen activator (tPA) to enhance thrombolytic therapy. This biomimetic nanovesicle was constructed through simple self-assembly with thioketal linker-containing lipids for microenvironment response, decorated with fibrinogen-derived peptides for targeting, and surface-coated with 2,2,6,6-tetramethylpiperidin-1-oxyl for enhanced magnetic resonance (MR) contrast. In vitro static and microfluidic studies confirmed the specific binding to activated platelets and efficient thrombus targeting under a flow condition. Efficient thrombus microenvironment response and triggered tPA release was demonstrated, thus leading to effective thrombolysis under both static and flow conditions. Intravenous administration in vivo enabled prolonged circulation, enhanced thrombus accumulation and MR imaging. In a rat carotid thrombosis model, tPA@THPTN outperformed free tPA and non-targeted controls, achieving complete clot dissolution in 120 min with minimal hemorrhage risk. This biomimetic platform offers a potent theranostic strategy for thrombosis.
Date Issued
2026-03-10
Date Acceptance
2026-01-11
Citation
Journal of Controlled Release, 2026, 391
ISSN
0168-3659
Publisher
Elsevier
Journal / Book Title
Journal of Controlled Release
Volume
391
Copyright Statement
Copyright © 2026 Elsevier B.V. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41534714
PII: S0168-3659(26)00031-3
Subjects
Effective thrombolysis
Honeybees finding nectars
Magnetic resonance imaging
Specific thrombus targeting
Thrombus microenvironment response
Publication Status
Published
Coverage Spatial
Netherlands
Article Number
114630
Date Publish Online
2026-01-12