PUBLICATION
Smart hypoxia-responsive sulfated polysaccharides liposomes for controlled and targeted urokinase delivery in thrombotic therapy
- Authors
- Wang, D., Li, D., Liu, X., Wang, S., Fan, Y., Lu, L., Shen, C., Li, C.
- ID
- ZDB-PUB-260203-1
- Date
- 2026
- Source
- Journal of controlled release : official journal of the Controlled Release Society : 114669114669 (Journal)
- Registered Authors
- Lu, Ling
- Keywords
- Hypoxia-responsive, P-selectin targeting, Targeted delivery, Thrombolytic therapy, Urokinase
- MeSH Terms
-
- Animals
- Blood Platelets/drug effects
- Blood Platelets/metabolism
- Delayed-Action Preparations
- Drug Delivery Systems
- Drug Liberation
- Fibrinolytic Agents*/administration & dosage
- Fibrinolytic Agents*/therapeutic use
- Humans
- Liposomes
- Male
- Mice
- P-Selectin/metabolism
- Polysaccharides*/administration & dosage
- Polysaccharides*/chemistry
- Sulfates/chemistry
- Thrombosis*/drug therapy
- Urokinase-Type Plasminogen Activator*/administration & dosage
- Urokinase-Type Plasminogen Activator*/therapeutic use
- Zebrafish
- PubMed
- 41621757 Full text @ J. Control Release
Citation
Wang, D., Li, D., Liu, X., Wang, S., Fan, Y., Lu, L., Shen, C., Li, C. (2026) Smart hypoxia-responsive sulfated polysaccharides liposomes for controlled and targeted urokinase delivery in thrombotic therapy. Journal of controlled release : official journal of the Controlled Release Society. :114669114669.
Abstract
Thrombosis remains a leading cause of cardiovascular and cerebrovascular mortality worldwide. Plasminogen activators, notably urokinase and alteplase, have been established as standard thrombolytic agents in clinical practice. However, their therapeutic potential is severely compromised by rapid metabolic clearance, non-specific biodistribution, and associated hemorrhagic complications. Here, we designed a dual-functional nano drug delivery platform that leverages P-selectin overexpression on activated platelets and the characteristic hypoxic microenvironment at thrombotic sites for precision thrombolytic intervention. Specifically, we developed a hypoxia-responsive block (PAC) by conjugating polyguluronate sulfate (PGS, P-selectin targeting motif) with azobenzene-modified cholesterol, enabling urokinase encapsulation within PAC@UK liposomes. Under hypoxic conditions that mimic the thrombotic microenvironment, the reductive cleavage of azobenzene moieties initiated sustained urokinase release (96.41% cumulative release), while maintaining exceptional biocompatibility and demonstrating preferential targeting of activated platelets. Comprehensive in vivo validation across zebrafish, murine mesenteric, and carotid artery thrombosis models revealed markedly enhanced thrombolytic efficacy compared to free UK. This biomimetic nanoplatform represents a paradigm shift toward intelligent, site-specific thrombolytic intervention, offering substantial clinical promise for safer and more effective treatment of thrombotic disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping