Implementation of a patient-derived 3D model of glioblastoma multiforme for the developing ofextracellularvesicles-based drug delivery system (EXANDROIDEX-EXtracellular vesicles pAtieNt-DeRived 3d gbmmOdel drug delIvery Developing)

PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR)

Missione 4 - Componente 2 - Investimento 1.1

“Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN)” - Finanziato dall’Unione europea – NextGenerationEU

Bando PRIN 2022 PNRR

D.D. n. 1409 del 14.09.2022

Progetto: Implementation of a patient-derived 3D model of glioblastoma multiforme for the developing of extracellularvesicles-based drug delivery system (EXANDROIDEX-EXtracellular vesicles pAtieNt-DeRived 3d gbm mOdel drug delIvery Developing)

Acronimo: EXANDROIDEX

Codice Identificativo Progetto: P2022AFZSN - CUP: D53D23022640001

Cancer Glioblastoma (GBM) is a common aggressive form of brain cancer characterized by poor prognosis. Despite surgical resection and other available therapeutic treatments, patients often suffer from tumor relapse and succumb due to its rapid growth, chemoresistance, and high invasiveness. GBM tumors are highly heterogeneous, being composed of cellular and matrix components, which contribute to tumor cell invasion, cancer stem cell maintenance, and drug resistance. Novel anticancer strategies are constantly needed to overcome the drawbacks associated with GBM biology. This project aims to enhance the knowledge on GBM biology and heterogeneity, generating and validating a patient-derived 3D model of GBM, that will be studied for his genotypic and phenotypic features. It will develop a personalized drug delivery system, useful for precision medicine applications, based on patient plasma-derived EVs that will be engineered to specifically carry selected antitumor microRNAs (miRNAs), that will be shuttled to target oncogenes associated with this cancer. The GBM 3D model will be studied for the response to the therapeutic tool developed. To establish the GBM 3D model, cells will be obtained from surgical resection and cultured in coculture with astrocytes and micro endothelial cells in 3D conditions, using a platform that provide a more physiologically relevant environment, for the generation of uniform, size-controlled 3D cultures with organ-like microarchitecture and morphology. This model will enable us to overstep the disadvantages of the use of animal models and enable better understanding of the disease. Furthermore, it will be assayed for new targeted therapies based on engineered GBM-derived EVs, isolated from patients.
The use of cutting-edge technologies, such as the implementation of a novel 3D tissue-like model in vitro that recapitulates the heterogeneous microenvironment of GBM; the use proteomics approach and miRNAs profiling; the employment of patient derived EVs loaded with specific molecules, will ensure the achievement of the objectives foreseen in each work package. The multidisciplinary approach and the joint efforts of the Research Units with complementary expertise represent a truly unique opportunity in the field of brain cancer research in Italy, which will allow for significant improvements in GBM patients management.