RESUMO
Vascular stent is viewed as one of the greatest advancements in interventional cardiology. However, current approved stents suffer from in-stent restenosis associated with neointimal hyperplasia or stent thrombosis. Herein, we develop a nitric oxide-eluting (NOE) hydrogel coating for vascular stents inspired by the biological functions of nitric oxide for cardiovascular system. Our NOE hydrogel is mechanically tough and could selectively facilitate the adhesion of endothelial cells. Besides, it is non-thrombotic and capable of inhibiting smooth muscle cells. Transcriptome analysis unravels the NOE hydrogel could modulate the inflammatory response and induce the relaxation of smooth muscle cells. In vivo study further demonstrates vascular stents coated with it promote rapid restoration of native endothelium, and persistently suppress inflammation and neointimal hyperplasia in both leporine and swine models. We expect such NOE hydrogel will open an avenue to the surface engineering of vascular implants for better clinical outcomes.
Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Reestenose Coronária/prevenção & controle , Hidrogéis/farmacologia , Neointima/prevenção & controle , Óxido Nítrico/farmacologia , Stents , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Humanos , Hidrogéis/metabolismo , Hiperplasia , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Neointima/patologia , Óxido Nítrico/metabolismo , Coelhos , Suínos , Transcriptoma/efeitos dos fármacosRESUMO
By covalently connecting taxol with a motif that is prone to self-assemble, we successfully generate the precursor (5a), the hydrogelator (5b), and hydrogel of a taxol derivative without compromising the cytotoxic activity of the taxol. This approach promises a general method to create nanofibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself.
Assuntos
Fosfatase Alcalina/química , Antineoplásicos Fitogênicos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Nanoestruturas/química , Paclitaxel/química , Moduladores de Tubulina/química , Células HeLa , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/químicaRESUMO
Using Nalpha,Nalpha-bis(carboxymethyl)lysine to react with FePt magnetic nanoparticles, we synthesized the FePt-NTA conjugate, which immobilizes Ni2+ ions and selectively binds to histidine-tagged proteins at concentration as low as 0.5 pM. This simple system serves as a useful alternative to existing protocols for protein separation and also acts as a versatile agent for transporting and anchoring proteins.