Tesis de doctorado

Research and development of emerging technologies for exosome-based cancer diagnostics and therapeutics

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Abstract

Exosomes hold the potential to transform cancer nanomedicine. As cellular nanoparticles, exosomes shuttle biomolecules between cells and tissues, providing a unique platform for diagnosis and targeted therapy. The study of exosomes and their potential applications has gained significant attention, and a vast body of literature illustrates the potential of exosomes to improve cancer care. However, the clinical translation of exosome-based diagnostics and therapeutics faces several challenges. Limitations in exosome research include a lack of standardized protocols for exosome isolation, characterization, and functional analysis. Concerns about their efficacy and safety arise primarily from their biodistribution in vivo. Additionally, our understanding of their biology remains limited. Emerging technologies, particularly those capable of manipulating complex biological systems at the nanoscale, are proposed to overcome these limitations. Such technologies could potentially accelerate the development of novel therapeutic strategies in personalized and precision medicine through exosome-based products. Nevertheless, extensive proof of concept in multiple preclinical models is required to ensure clinical efficacy and to advance the translation of exosome-based products from bench to clinic. In this work, we present a multidisciplinary approach to address the challenges encountered in exosome isolation, therapeutic delivery, and functional analysis. We designed a microfluidic device based on dielectrophoresis for rapid, size-based exosome separation. For targeted delivery, we encapsulated exosomes in photocrosslinkable and biodegradable alginate hydrogels. To better understand exosome biology, we developed a 3D cell culture model and studied the effect of an inhibitor of exosome release on the expression and subcellular localization of molecular targets for cancer therapeutics.

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https://orcid.org/0000-0001-6734-8245

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