Cápsides virales como nanoacarreadores enzimáticos para quimioterapia

Abstract

La encapsulación de enzimas dentro de cápsides virales llamadas "virus-like particles" (VLPs) o dentro de otro tipo de cajas proteicas es un tema de rápido desarrollo debido a sus implicaciones en biocatálisis así como su potencial uso como sistemas para el suministro controlado de enzimas. Aquí se reporta la encapsulación de un citocromo P450 (CYP) que pertenece a una familia de enzimas de importancia médica.

The encapsulation of enzymes inside virus-like nanoparticles (VLPs) or other protein cages has been a fast growing topic because of its implications in biocatalysis as well as their potential as enzymatic delivery systems. We report here the encapsulation of a CYP450 which belong to a family of enzymes medically important. A variant of CYPBM3 from Bacillus megaterium, that has been evolved for enhanced peroxidase activity, was assayed for encapsulation. This CYP variant was effectively encapsulated in VLPs constituted of coat protein from cowpea chlorotic mottle virus (CCMV). The catalytic VLPs are able to transform the chemotherapeutic pro-drug, tamoxifen, and the emerging pro-drug resveratrol. The chemical nature of the products was identified, confirming similar active products than those obtained with human CYP. The enzymatic VLPs remain stable after the catalytic reaction. The aim and innovation of this work is to make more efficient chemotherapy drugs activating them mainly in the target tissue avoiding the dramatic side effects and reducing the doses. The encapsulation of this CYP450 in viral structures will provide a model for the design of biocatalytically nanoparticles with potential medical applications.