RESUMO
Many antitumor drugs have a limited ability to penetrate more than a few cell diameters from blood vessels into solid tumors, which limits their effectiveness. In this study, we investigated whether the biological activity of endostatin can be enhanced by the addition of an integrin-targeting and permeability-enhancing sequence. The internalization RGD (CRGDKGPDC; iRGD) sequence was added at the carboxyl terminus of endostatin. Modification of endostatin with the iRGD motif showed specific and increased binding to endothelial cells; the increased binding correlated with an improved antiangiogenic property. iRGD-modified endostatin was more effective than human endostatin in inhibiting liver cancer growth in athymic mice. The finding indicates that addition of a vascular targeting and permeability sequence can enhance the biological activity of an antiangiogenic molecule and tumor targeting.
Assuntos
Endostatinas/administração & dosagem , Endostatinas/farmacocinética , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Sequência de Bases , Permeabilidade Capilar , Bovinos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/farmacocinética , Embrião de Galinha , Endostatinas/genética , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Integrinas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Oligopeptídeos/genética , Ligação Proteica , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacocinéticaRESUMO
Nitrobenzene is one of the toxic compounds. Much work had focused on biodegradation of it sofar. Two main pathways for nitrobenzene biodegradation, oxidative and partial reductive pathways, were reviewed in this article. The mechanism of these pathways including involved enzymes and genes was introduce in details. Comparative analysis of the pathways would provide basis for the development and application of biodegradation technology for nitrobenzene and other organic pollutants.