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1.
J Nanobiotechnology ; 22(1): 593, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39343894

RESUMEN

By inhibiting acetylcholinesterase (AChE) activity, organophosphate compounds (OPs) can quickly cause severe injury to the nervous system and death, making it extremely difficult to rescue victims after OP exposure. However, it is quite challenging to construct scavengers that neutralize and eliminate these harmful chemical agents promptly in the blood circulation system. Herein, we report an enzyme-armed biomimetic nanoparticle that enables a 'targeted binding and catalytic degradation' action mechanism designed for highly efficient in vivo detoxification (denoted as 'Nanocleaner'). Specifically, the resulting Nanocleaner is fabricated with polymeric cores camouflaged with a modified red blood cell membrane (RBC membrane) that is inserted with the organophosphorus hydrolase (OPH) enzyme. In such a subtle construct, Nanocleaner inherits abundant acetylcholinesterase (AChE) on the surface of the RBC membrane, which can specifically lure and neutralize OPs through biological binding. The OPH enzyme on the membrane surface breaks down toxicants catalytically. The in vitro protective effects of Nanocleaner against methyl paraoxon (MPO)-induced inhibition of AChE activity were validated using both preincubation and competitive regimens. Furthermore, we selected the PC12 neuroendocrine cell line as an experimental model and confirmed the cytoprotective effects of Nanocleaner against MPO. In mice challenged with a lethal dose of MPO, Nanocleaner significantly reduces clinical signs of intoxication, rescues AChE activity and promotes the survival rate of mice challenged with lethal MPO. Overall, these results suggest considerable promise of enzyme-armed Nanocleaner for the highly efficient removal of OPs for clinical treatment.


Asunto(s)
Acetilcolinesterasa , Inhibidores de la Colinesterasa , Compuestos Organofosforados , Animales , Acetilcolinesterasa/metabolismo , Ratones , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Ratas , Compuestos Organofosforados/química , Membrana Eritrocítica , Células PC12 , Paraoxon/toxicidad , Paraoxon/análogos & derivados , Nanopartículas/química , Arildialquilfosfatasa/metabolismo , Arildialquilfosfatasa/química , Masculino , Intoxicación por Organofosfatos/tratamiento farmacológico
2.
Biomed Mater ; 19(6)2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39208842

RESUMEN

Medical dressings with multifunctional properties, including potent regeneration capability and good biocompatibility, are increasingly needed in clinical practice. In this study, we reported a novel hybrid wound dressing (PCL/SerMA/DMOG) that combines electrospun PCL membranes with DMOG-loaded methacrylated sericin (SerMA) hydrogel. In such a design, DMOG molecules are released from the hybrid dressing in a sustained mannerin vitro. A series ofin vitroassays demonstrated that DMOG-loaded hybrid dressing has multiple biological functions, including promotion of human umbilical vein endothelial cells proliferation and migration,in vitrovascularization, and the generation of intracellular NO. When applied to the cutaneous wound, the PCL/SerMA/DMOG dressing significantly accelerated wound closure and tissue regeneration by promoting angiogenesis in the wound area, collagen deposition, and cell proliferation within the wound bed. These results highlight the potential clinical application of PCL/SerMA/DMOG hybrid dressings as promising alternatives for accelerating wound healing via improved biocompatibility and angiogenesis amelioration.


Asunto(s)
Vendajes , Materiales Biocompatibles , Proliferación Celular , Células Endoteliales de la Vena Umbilical Humana , Poliésteres , Sericinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Humanos , Poliésteres/química , Proliferación Celular/efectos de los fármacos , Animales , Sericinas/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Piel/lesiones , Piel/metabolismo , Hidrogeles/química , Neovascularización Fisiológica/efectos de los fármacos , Masculino , Movimiento Celular/efectos de los fármacos , Ratones , Ratas , Ratas Sprague-Dawley , Metacrilatos/química , Ensayo de Materiales
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