Δηλώνω ότι έλαβα γνώση και ανεπιφύλακτα συμφωνώ και αποδέχομαι τους
Despite the advances and extensive research on novel approaches for cancer therapeutics, confronting cancer still remains a challenge in the fields of biomedical/molecular research, molecular pharmacology and drug delivery. In that context, natural systems and endogenous delivery sources, like exosomes, seem to denote valuable tools in cancer therapeutics. Nowadays, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Exosomes as mimics of “nature’s delivery systems” allow for the delivery of biological molecules such as therapeutic recombinant proteins and nucleic acids which constitute some of the newer drug candidates, to various target tissues, as the former are non-immunogenic in nature due to similar composition as body's own cells. Exosomes are also promising vehicles for the delivery of microRNAs (miRNAs) and small interfering RNAs (siRNAs). Within these frames, in the present work, we have focused on ...
Despite the advances and extensive research on novel approaches for cancer therapeutics, confronting cancer still remains a challenge in the fields of biomedical/molecular research, molecular pharmacology and drug delivery. In that context, natural systems and endogenous delivery sources, like exosomes, seem to denote valuable tools in cancer therapeutics. Nowadays, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Exosomes as mimics of “nature’s delivery systems” allow for the delivery of biological molecules such as therapeutic recombinant proteins and nucleic acids which constitute some of the newer drug candidates, to various target tissues, as the former are non-immunogenic in nature due to similar composition as body's own cells. Exosomes are also promising vehicles for the delivery of microRNAs (miRNAs) and small interfering RNAs (siRNAs). Within these frames, in the present work, we have focused on: i) the development of exosome-based delivery systems, derived from cells growing in culture, as well as the physicochemical and molecular characterization of these delivery platforms, and ii) the pharmacological evaluation of exosomes as therapeutic biomolecule carriers in the context of cancer therapeutics. More specifically, the first objective of this project was the isolation of exosomes utilizing stable cell lines growing in culture followed by the detailed physicochemical characterization and the molecular profiling of the derived vesicles. To this end, we utilized well established physicochemical techniques, widely used for the study of conventional new drug delivery systems, as well as innovative techniques in order to unravel exosome proteome profile and lipid identity. Moreover, we attempted to pharmacologically exploit and further assess exosome capability as innovative small RNA ‘bio-shuttles’, utilizing both normal and cancer cell lines as exosome recipients. The aims of this approach were: i) the elucidation of the main factors that affect the selectivity process upon the uptake of exosomes by various cell lines in culture, ii) the development of ‘ideal’ exosome-based delivery carriers derived from specific donor cell lines that could be potentially used for various pathological tissue sites, iii) the further assessment of exosome loading capability with molecular cargo as well as the examination of any time-dependent effect on cargo encapsulation into exosomes and, finally, iv) the evaluation of exosome capability in delivering molecular cargo intracellularly in a versatile set of cell types. The results confirmed the efficient development of exosomal systems utilizing the cell lines under study, and suggest the potential utility of these exosome vehicles as innovative, efficient and selective delivery systems for small DNA and RNA molecules in the context of therapeutics. Moreover, the results highlighted that exosomes derived from the cell lines under examination, possess the potential to be pharmacologically exploitable as innovative small RNA ‘bio-shuttles’ with various applications as targeted therapeutics and theranostics within the concept of nanomedicine and precision medicine.
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