Project: New Approaches to Rare Respiratory Orphan fibrotic diseases With locally administered targeted NANOparticles

Acronym	ARROW-NANO (Reference Number: EURONANOMED2017-127)
Duration	01/03/2018
Project Topic	The present project aims at developing a new treatment of two rare severe respiratory disorders, bronchiolitis obliterans syndrome (BOS) and Systemic Sclerosis-Interstitial Lung Disease (SSC-ILD) by using nanovectors loaded with drugs and targeted specifically to diseased cells. Conventional systemic treatments of these fibrotic disorders are poorly effective due to insufficient drug accumulation, limited efficacy and high toxicity. We have demonstrated in vitro that drugs loaded into specifically targeted (coated with anti CD44 antibody) gold nanoparticles (GNPs) were more effective in inhibiting primary pathological cells (from BOS and SSC-ILD) than lone drugs, without affecting normal airway epithelium. The same GNPs administered to normal mice by inhalation selectively localized in the lungs without peripheral toxicity. When tested on a mouse model of pulmonary fibrosis (intratracheal administration) these GNPs were effective in preventing pulmonary fibrosis. However, long-term treatment might result in accumulation of GNPs in macrophages suggesting that chronic administration may cause excessive gold store. The aim of this project is to engineer novel, fully biocompatible targeted nanovectors (liposomes) that can be safely and repeatedly administered by inhalation. To do this, consortium will: 1) manufacture liposomes functionalized with ligands targeting CD442) screen in vitro efficacy/toxicity of the novel liposomes compared with lone drugs or drug loaded-GNPs3) determine biodistribution, efficacy, and toxicity of the novel liposomes in animal models of BOS and SSc-ILD4) plan a translation from the bench results to phase I clinical trials in both diseases. This project takes advantage of the complementary competences of the partners and their already existing collaboration. The design and fabrication of nanovectors bears high innovation potential and the consortium has already foreseen intellectual property rights protection and commercialization
Network	EuroNanoMed III
Call	Joint Transnational Call for Proposals (2017) for “European Innovative Research & Technological Development Projects in Nanomedicine”

Project partner

Number	Name	Role	Country
1	IRCCS POLICLINICO SAN MATTEO FOUNDATION (PMSF)	coordinator	Italy
2	Centre National de la Recherche Scientifique (CNRS)	Partner	France
3	HOSPITAL UNIVERSITARIO DE LA PRINCESA, IIS-IP, MADRID	Partner	Spain
4	Medical University of Vienna	Partner	Austria