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.
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Funding SchemeERC-STG - Starting Grant
1099 085 Lisboa