Project description DEENESFRITPL Recruiting exosomes for drug delivery to the lung Exosomes are extracellular vesicles generated from all cells and carry various biomolecules including DNA, lipids and proteins. Their endogenous origin helps them evade immune recognition while their ability to deliver payload at specific target sites renders them ideal for drug delivery. The EU-funded BESG project will engineer exosomes from mesenchymal stem cells to specifically target non-small cell lung carcinoma (NSCLC). The exosomes will deliver an EGFR inhibitor and a specific siRNA against NSCLC and metastasis. Using advanced imaging techniques, scientists will evaluate the pharmacokinetics, biodistribution and anti-cancer activity of exosomes in a mouse model of the disease. The project's results will serve as the foundation for the clinical testing of bioengineered exosomes as a treatment option for lung cancer. Show the project objective Hide the project objective Objective ABSTRACT: Lung cancer is the principal cause of cancer-related death around the world and has become more predominant among former than current smokers. Smoking, alcoholism, air pollution, occupational exposure are among the main causes of non-small cell lung cancer (NSCLCs). It is difficult to simultaneously deliver therapeutics and nucleic acid to the target site. With the advancement of nanotechnology, a delivery system composing of cellular proteins which can bypass the reticuloendothelial system (RES) and have the ability to release payload at the specific target site is the necessity of the current era. Exosomes (Exo) are clinically acceptable, having protein membrane composition and the ability to deliver payload at specific target sites. Having endogenous origin, Exo evade immune recognition and clearance compared to exogenous nanovesicles. Exo are natural carriers of nucleic acids and they can be engineered to deliver siRNA as well as anti-cancer drugs. In this we propose the conjugation or covering of mesenchymal stromal cells (MSCs) derived exosomes with HSP4 peptide (target specific to NSCLCs) and loading them with Gefitinib (GEF), an EGFR inhibitor and SPC24 siRNA (target for NSCLCs and metastasis). The delivery of GEF and SPC24 siRNA using bioengineered exosomes (BESG) will reduce their dosage; improve patient compliance and life expectancy of patients. BESG will be evaluated for their uptake mechanisms and their mechanism of action in cell culture models of NSCLCs. BESG will specifically target the NSCLCs and release its payloads at cancer site. The underlying mechanisms, pharmacokinetics, biodistribution and anti-cancer activity will be evaluated in xenograft model of NSCLCs using advance imaging technologies. The BESG developed during this program will have a clinical potential and the trainings obtained through this program will help in career advancement in the area of drug delivery and precision medicine. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsmedical and health sciencesclinical medicineoncologylung cancernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologymedical and health scienceshealth sciencespersonalized medicine Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF-EF-SE - Society and Enterprise panel Coordinator PERCUROS BV Net EU contribution € 175 572,48 Address Eerbeeklaan 42 2573 HT 's-gravenhage (den haag) Netherlands See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region West-Nederland Zuid-Holland Agglomeratie ’s-Gravenhage Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
