Remote control of multiple cell functions through multi-stimuli-responsive nanoparticle assemblies

Descripción del proyecto

Control remoto de células para el futuro de la medicina

Imagínese poder activar, silenciar o redirigir células del interior de su cuerpo con solo pulsar un botón, con la misma facilidad con la que se sintoniza una radio. El proyecto CELL-NANO-REMOTE, financiado por el Consejo Europeo de Investigación, pretende hacerlo realidad. Inspirándose en campos como la optogenética y la magnetogenética, el proyecto pretende lograr el control remoto de múltiples funciones celulares a la vez. En concreto, combina nanopartículas inteligentes que responden a estímulos con ingeniería genética avanzada para crear células que respondan a la luz, los campos magnéticos o los ultrasonidos de formas específicas. Los investigadores utilizarán estas señales para guiar a las células en la realización de tareas complejas en tiempo real. La tecnología podría transformar la inmunoterapia, la medicina regenerativa y la biotecnología.

Objetivo

CELL-NANO-REMOTE aims to achieve flexible, remote control over therapeutic cell behaviour. In previous work in optogenetics and magnetogenetics, only partial remote cell control has been attained using light or magnetic fields as triggers. Furthermore, these approaches are generally limited to single cell responses, typically influencing one particular gene, receptor, or ion channel. In contrast, CELL-NANO-REMOTE seeks to obtain independent control over various cell functions without cross-activation upon application of external stimuli (light, magnetic fields or ultrasound).

To surpass the limitations of current strategies and achieve the ambitious goal of the project, CELL-NANO-REMOTE combines various stimuli-responsive nanoparticles (NPs) and genetic engineering as ex vivo modification tools of the target cells. To ensure uniform and simultaneous uptake of all the different NPs by cells, they will be assembled into multi-NP assemblies. These multi-NP assemblies will be characterized by nano flow cytometry, a novel technique which enables optimization of assembly conditions to ensure the desired ratio of each component. In response to the application of external stimuli, the NPs will release different cargos inside the engineered cells, providing control over various cell functions. To demonstrate the potential of this approach to improve cell therapies, the project will unfold in two stages: a proof-of-concept stage using a model cell line followed by a second stage showcasing two case studies, in immunology and in regenerative medicine.

The CELL-NANO-REMOTE approach will offer flexible, real-time command of cell behaviour, allowing for adaptable and dynamic control of cell responses. This remote-control system could revolutionize how we manipulate therapeutic cells, offering significant advancements for a wide range of pathologies. Furthermore, this strategy will have applications not only in cell therapy, but also in biotechnology more broadly.