BESG · Bioengineered exosomes based approaches for the effective treatment of non-small cell lung cancer
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-10-01 → 2022-09-30
- EU contribution
- €175,572
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Bioengineered exosomes based approaches for the effective treatment of non-small cell lung cancer
The most prevalent type of lung cancers are non-small cell lung cancers (NSCLCs), which have a variety of pathological characteristics. NSCLCs have been identified as a collection of different diseases with cellular and genetic heterogeneity by detailed investigations of lung cancer genomes and signalling pathways during the past ten years (Chen Z. et al. 2014). 85% of lung cancer cases in the United States are NSCLCs. The epidemiology has identified smoking, air pollution, occupational exposure, and alcohol consumption as the main risk factors. At the time of diagnosis, it was discovered that 70% of patients had locally progressed or metastatic disease (Molina JR. et al. 2008). The progression of NSCLCs is influenced by a number of driver mutations, including ROS1, RET, and other translocations; EGFR mutations; KRAS mutations; BRAF mutations; MET splice site mutations (Hirsch, FR., et al 2016). The treatment of lung cancer is drastically altering as a result of targeted medicines. These treatments include pharmaceuticals or biologicals that target immune checkpoint inhibitors, anti-apoptotic molecules implicated in cancer cell survival and proliferation, and driver mutation-targeting agents. With the introduction of new drugs, targets, therapeutic combinations, and drug delivery methods, the field of targeted therapeutic research is advancing every day (Molina JR. et al. 2008). "BESG" sought to create a therapeutic drug delivery system prototype with improved targeting capabilities for treating non-small cell lung cancer using exosomes modified with the a targeting peptide and loaded with small molecule and nucleic acid. Theranostic and therapeutic agent delivery methodologies were also combined by BESG in order to create advanced drug delivery systems that may one day be used to develop personalized medicines. The overall objectives of "BESG" includes a. Development of smart peptide functionalized exosome loaded with small molecule and nucleic acid and/or fluorescent dye b. Characterization of developed products for their enhanced targeting capabilities, cytotoxicity with NSCLCs c. Functional studies of developed products in the animal model of NSCLCs.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- PERCUROS BV · 's-Gravenhage (Den Haag)CoordinatorNetherlands
Links
Data: CORDIS, © European Union