Cancer heterogeneity and therapy profiling using bioresponsive nanohydrogels for the delivery of multicolor logic genetic circuits.

Descripción del proyecto

Una plataforma de nanopartículas para el análisis de tumores

En los últimos años, se ha producido un aumento notable en el empleo de nanomateriales para el tratanóstico del cáncer. Con todo, las barreras fisiológicas del microentorno tumoral, así como la heterogeneidad tumoral, plantean limitaciones importantes para el tratamiento y la terapia. Los científicos del proyecto GelGeneCircuit, financiado con fondos europeos, se proponen investigar cómo responden los tumores al tratamiento, así como los factores subyacentes a la heterogeneidad observada. Para ello, desarrollarán una plataforma basada en hidrogel para suministrar nanopartículas que ayudarán al análisis de tumores. Su objetivo es emplear este método para identificar nuevas dianas biológicas y estudiar mecanismos moleculares fundamentales que sean útiles para diseñar tratamientos antineoplásicos eficaces.

Objetivo

Conventional cancer therapies suffer from poor efficacy owing to the lack of efficient delivery systems and to the inherent tumor heterogeneity that requires multi-modal approach to abrogate cancer progression. Nanotechnology holds promise to address these drawbacks, as the use of (bio)nanomaterials for diagnostics and therapy has been gaining momentum over the last years. The main goal of this project is to develop a novel and facile platform capable of profiling both the therapy outcome and heterogeneity in cancer, by using bioresponsive nanohydrogels for the delivery of logic multicolor synthetic gene circuits. These logic synthetic gene circuits will be designed as a biobarcode of multicolor RNA circuits embedded in hybrid nanoparticles and doped in hydrogels for local therapy in breast cancer in vivo. Using cell-type specific promoters, the multicolor miRNA circuits will be expressed specifically to each type of the cells of the tumor microenvironment. Subsequently, this will permit to evaluate the therapeutic efficacy in a cell-by-cell basis and to profile the tumor heterogeneity across different breast cancer types. In order to potentiate the translation of this ground-breaking platform into clinics and precision medicine, novel de-regulated miRNA targets will be identified based on screens performed in breast cancer patient-derived tumors that better reflect the heterogeneous tumor microenvironment in a patient-by-patient basis.
In sum, the material platforms developed herein and newly identified biological targets can be harnessed to design effective cancer treatments that go beyond breast cancer. The project is highly versatile and multidisciplinary and this system can be easily adapted to target any cancer cell type and molecular mechanisms and translated to clinical testing.