RESUMO
A novel graphene quantum dot (GQD)@Fe3O4@SiO2 based nanoprobe was reported for targeted drug delivery, sensing, dual-modal imaging and therapy. Carboxyl-terminated GQD (C-GQD) was firstly conjugated with Fe3O4@SiO2 and then functionalized with cancer targeting molecule folic acid (FA). DOX drug molecules were then loaded on GQD surface of Fe3O4@SiO2@GQD-FA nanoprobe via pi-pi stacking, which resulted in Fe3O4@SiO2@GQD-FA/DOX conjugates based on a FRET mechanism with GQD as donor molecules and DOX as acceptor molecules. Meanwhile, we successfully performed in vitro MRI and fluorescence imaging of living Hela cells and monitored intracellular drug release process using this Fe3O4@SiO2@GQD-FA/DOX nanoprobe. Cell viability study demonstrated the low cytotoxicity of Fe3O4@SiO2@GQD-FA nanocarrier and the enhanced therapeutic efficacy of Fe3O4@SiO2@GQD-FA/DOX nanoprobe for cancer cells. This luminomagnetic nanoprobe will be a potential platform for cancer accurate diagnosis and therapy.
Assuntos
Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Óxido Ferroso-Férrico/química , Grafite/química , Neoplasias/tratamento farmacológico , Pontos Quânticos/química , Dióxido de Silício/química , Antibióticos Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Monitoramento de Medicamentos/métodos , Fluorescência , Transferência Ressonante de Energia de Fluorescência/métodos , Células HeLa , Humanos , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Pontos Quânticos/ultraestruturaRESUMO
Oxymatrine (OMT) is a major bioactive component derived from Sophora flavescens Ait (kushen), which is widely used in Chinese medicine. Recent studies have shown that it has neuroprotective effects; however, its underlying mechanisms remain unclear. We focus on the mechanisms of pharmacologic action in OMT by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro. OMT prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion, in vivo. In vitro cultured neurons challenged with N-methyl-D-aspartate (NMDA, 200 µM) for 30 min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure. Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro- and anti-apoptotic proteins. Furthermore, OMT significantly reversed the up-regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA. OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family. Our results provide new insights into the development of natural therapeutic anti-oxidants against ischemia.
