Project description
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.
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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- medical and health sciences clinical medicine oncology lung cancer
- natural sciences biological sciences cell biology
- medical and health sciences health sciences personalized medicine
- medical and health sciences basic medicine pharmacology and pharmacy pharmacokinetics
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
2573 HT 's-Gravenhage (Den Haag)
Netherlands
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.