Development of a biotechnological nanoparticle platform for the delivery of antitumor therapies using Patient Derived-Organoid library of Breast Cancer

In this project, we propose to realize an integrated bionanoparticle (BNP) platform exploiting biological-derived anocages – consisting of protein (H-Ferritin, vaults), DNA or extracellular vesicles, loaded with antitumor drugs, Chk1 inhibitors or siRNA, and modified to address receptors overexpressed on TNBC cell surface – as innovative therapeutic approach for triple negative breast cancer (TNBC). Different therapeutic approaches will be combined into a triple-target strategy: 1) inhibition of EGFR nuclear translocation; 2) blockage of Chk1 pathway; 3) chemotherapeutics-mediated DNA damage, combined with inhibition of Chk1). The BNP platform will be tested on 2D cell lines and in a Patient-Derived Organoid (PDO) system, which represents a reliable preclinical disease model alternative to conventional in vivo studies. To this aim, a TNBC PDO model to finalize and validate the utility of our proposed multitasking BNP platform will be employed. By exploiting targeted nanodrugs, the use of BNPs could here increase antitumor efficacy and decrease chemoresistance. For cell targeting strategies, we will take advantage of two well-characterized receptors, namely EGFRvIII and FOLR1. We will also exploit the high expression of TfR1 as an additional target for H-Ferritin in TNBC cells.