Descripción del proyecto
El análisis de proteasas extracelulares contribuye al diagnóstico basado en proteasas y tratamientos específicos para tumores
Las proteasas son enzimas, es decir proteínas, que dividen o disgregan otras proteínas. Tienen funciones esenciales en el cuerpo sano. Algunas proteasas extracelulares también desempeñan un papel fundamental en la progresión de los tumores. Supervisar la actividad de las proteasas en vivo podría contribuir a realizar diagnósticos, pronósticos y tratamientos, pero es difícil hacerlo con sensibilidad y selectividad elevadas. El proyecto PROTECT, financiado con fondos europeos, abordará este desafío con una plataforma exclusiva integral para el diagnóstico y el tratamiento personalizado del cáncer. Permitirá supervisar la actividad de las proteasas para obtener las características de proteasa específicas de los tumores y administrar fármacos de forma específica.
Objetivo
Proteases are involved in all hallmarks of cancer and are key regulators of tumor progression. The difficulties to monitor protease activity in vivo with sufficient sensitivity and selectivity make development of protease targeting cancer drugs and implementation of protease activity as a diagnostic and prognostic biomarker very challenging. The aim of PROTECT is to develop a novel comprehensive protease activity profiling platform for cancer-associated extracellular proteases that can address the main limitations of current strategies for in vivo protease activity monitoring with the ambition to enable a dramatic increase in sensitivity and multiplexing capabilities. We will design Liposomal Activity-Based Sensors (LABS) that can amplify proteolytic cleavage by triggering release of liposome encapsulated synthetic biomarkers. We will further leverage the possibilities to extract tumor specific protease profiles for development of personalized protease-triggered liposomal drug delivery vehicles (PROVES) for precision medicine. Sophisticated protease-responsive membrane active peptides (proMAPs) will be developed to couple protease activity to biomarker and drug release. Methods to correlate biomarker release patterns to protease activity profiles in 3D breast cancer models will be explored. The PROTECT platform can then rapidly be repurposed for precision drug delivery. The PROVES concept will combine the excellent properties of liposomes for drug delivery and the optimal combination of proMAPs, based on the protease activity profile retrieved from the LABS, for optimized protease-triggered liposomal drug release. Combined, the LABS and PROVES concepts represent a unique and comprehensive platform for diagnostics and personalized cancer therapy. The proposed work goes far beyond stat-of-the-art and will address a significant and real bottleneck that hampers drug development and exploitation of proteases as diagnostics and prognostic cancer biomarkers.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
581 83 Linkoping
Suecia