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ROS-responsive Phenylboronic ester-based nanovesicles as multifunctional drug delivery systems for the treatment of inflammatory and thrombotic complications

Yu Xia,Runhai Chen,Ye Ke,Qiaoyi Han,Zhifang Ma,Qiang Shi

Inflammatory and thrombotic complications, and low loading of dual drugs with different hydrophilicity remain challenges to treat thrombosis with drug delivery systems (DDS). Here, the reactive oxygen species (ROS)-responsive amphiphilic block polymer poly(ethylene glycol)-b-2-((((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)carbonyl)oxy)ethyl methacrylate (PEG-b-PTBEM) is synthesized. And the nanovesicles (PPTV) are prepared successfully for the drug delivery platform by controlling the hydrophilic/hydrophobic ratio of molecular chains and molecular self-assembly. The anti-inflammatory drug indomethacin (IDM) is loaded in the wall of nanovesicels and the thrombolytic enzyme nattokinase (NK) is encapsulated in the aqueous cavity of nanovesicles. Both drugs can be rapidly released in the site of thrombus and/or inflammation with excessive ROS concentration. The dual drug-loaded nanovesicles not only eliminate ROS, but also alleviate inflammation and dissolve generated thrombus, showing significant therapeutic efficacy in the in-vivo mouse model of carrageenan tail thrombosis. Therefore, drug-delivery nanovesicles play multiple roles in the treatment of inflammation-induced thrombotic disorders, which offers a promising treatment for inflammatory and thrombotic complications.