PRIN 2017 - 2017E3A2NR - Marco Severgnini (DSB.AD008.533)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of biomedical technologies (ITB)

Project manager

MARCO SEVERGNINI
Phone number: 02 26422705
Email: marco.severgnini@itb.cnr.it

Abstract

Bionanoparticles (BNPs) stand at the forefront of emerging technologies for application in materials and life sciences, promising great potential in the development of innovative diagnostic imaging agents and drug delivery systems.
In this project, we propose to realize an integrated bionanoparticle platform exploiting biological-derived, conveniently-modified nanocages, consisting of protein (H-Ferritin, vaults), DNA or extracellular vesicles, loaded with antitumor drugs, Chk1 inhibitors or siRNA, as innovative therapeutic approach for triple negative breast cancer (TNBC). Different therapeutic approaches will be combined: 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 cell lines and in a Patient-Derived Organoid (PDO) system, which represents a reliable preclinical disease model. 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 increase anti-tumor efficacy and decrease chemoresistance.

Goals

Specific aims of the project are:
1) Development of a bionanoparticles (BNP) platform for drug delivery based on proteins, nucleic acids, and extracellular vesicles. Specific tasks will be: synthesis, characterization and surface decoration, loading of drug cargo and release assessment of BNP
2) Development of a patient-derived organoid model for triple-negative breast cancer (TNBC PDO)
3) Validation of BNPs in in vitro 2D TNBC cell lines and in PDOs. BNP anti-tumor efficacy will be assessed by a combination of chemical-physical, cellular and transcriptome sequencing evaluations, including single-cell state-of-the-art transcriptomics.
An outcome of the project will be improving our knowledge on the molecular mechanisms regulating the network of interactions among chemotherapeutics, drugs and the active pathways of signaling and proliferation in malignant cells. In addition, we aim to translate biochemical and cell biology information in clinical application, integrating scientific research and medical expectations. Moreover, we aim to stimulate an interdisciplinary collaboration setting the emergence of an innovation ecosystem around nanomedicine and TNBC research.

Start date of activity

21/05/2019

Keywords

Nanoparticelle, Carcinoma, Mammario

Last update: 03/08/2025