Fucose-Based Glycopolymeric Nanomicelles for Activated Platelet-Targeted Photothermal Thrombolysis.

Abstract

Thrombotic disorders represent a significant global health burden, with conventional thrombolytic therapies often limited by systemic bleeding risks and inadequate thrombus specificity. To address these challenges, a biomimetic glycopolymer-based nanomicelle system is developed for precision thrombosis management. Utilizing reversible addition-fragmentation chain-transfer polymerization, a type of cationic glycopolymer is synthesized from dimethylaminoethyl methacrylate and fucose monomers, which self-assembles into core-shell nanomicelles. The hydrophilic corona features multivalent fucose clusters that selectively bind to P-selectin on activated platelets within the thrombi, enabling targeted accumulation, while the hydrophobic core encapsulates the photothermal agent indocyanine green (ICG), enhancing its aqueous solubility and photostability. Upon near-infrared (NIR) laser irradiation, the ICG-loaded glycopolymeric nanomicelle, ICG@D₂₀F₂₀ exhibits efficient photothermal conversion, generating localized hyperthermia to disrupt fibrin networks. This platform offers several advantages, including precise targeting, synergistic thrombolysis, and enhanced biocompatibility, thereby overcoming the limitations of traditional thrombolytics and providing a novel approach for minimally invasive, image-guided cardiovascular interventions.