Nanomedicines for cell reprogramming in tissue engineering and immunomodulation

Abstract

The main goal of this thesis has been the development of various RNA-based therapies to modulate cell phenotypes in two different disease contexts: cancer and tissue engineering. Given the poor cell-permeability of naked RNA molecules, as well as their short half-life in biorelevant media, a critical aspect of the work has been the design and development of biomaterial-based systems intended to overcome these limitations. On the one hand, we developed a nanocarrier capable of co-allocating RNAi and chemokines to revert the tumor immunosuppression mediated by myeloid derived suppressor cells. On the other hand, we investigated a new concept of gene-activated matrices (GAMs) activated with mRNA-encoded transcription factors (TFs) to direct stem cell chondrogenic and myogenic specification. We finally optimized GAM mechanics in order to enhance TF transfection and cell differentiation driven by TF overexpression.