The applications of microfluidic platforms for cancer research: the tumor microenvironment and drug delivery systems

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dc.contributor.authorPapera Valente, Karolina
dc.contributor.supervisorSuleman, Afzal
dc.contributor.supervisorBrolo, Alexandre Guimaraes
dc.date.accessioned2020-08-28T03:37:38Z
dc.date.copyright2020en_US
dc.date.issued2020-08-27
dc.degree.departmentDepartment of Mechanical Engineeringen_US
dc.degree.levelDoctor of Philosophy Ph.D.en_US
dc.description.abstractThis work describes the use of microfluidic technology and biomaterials in cancer research by mimicking the extracellular matrix (ECM) and development of drug delivery system. Initially, biomaterials such as Gelatin methacryloyl (GelMA) and collagen type I were combined to create a hydrogel composite able to mimic both healthy and cancerous ECM. The impact of the tumor microenvironment was analyzed by using the hydrogel inside of a pressurized microfluidic device and by tracking the movement of gold nanoparticles (GNPs). The GNPs showed a decrease in diffusion coefficient of 77% when analyzed in cancerous conditions. This investigation was further explored by analyzing the diffusion of charged GNPs in the same system, while also tracking cellular uptake. An inverse correlation between diffusion and cellular uptake was obtained for charged GNPs in breast cancer cells. Due to the tunable properties and biocompatibility of GelMA, this hydrogel was also employed in the development of pH-responsive drug delivery systems. Since GelMA contains a gelatin backbone, two responsive polymers (Polymers A and B) were synthesized. Microspheres of ~40 μm were fabricated in flow focusing microfluidic devices. Polymer A microspheres displayed a swelling increase of 167% in pH 6.0, while polymer B spheres showed a 296% swelling in pH 10. Considering the unique properties of the tumor microenvironment such as leaky vasculature and acid pH environment, polymer A was selected to be used in the production of nanocarriers. The behavior of this polymer in acidic environment illustrated its potential applicability as drug delivery systems to the tumor area. Polymer A nanogels displayed a uniform size of 74 ± 7 nm. Lastly, GNPs were added to the solution of polymer A, leading to the fabrication of GNPs-loaded nanogels, presenting a homogenous distribution of gold particles inside nanogels.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.urihttp://hdl.handle.net/1828/12039
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectMicrofluidicsen_US
dc.subjectBiomaterialsen_US
dc.subjectECMen_US
dc.subjectIn vitro Modelen_US
dc.subjectCanceren_US
dc.titleThe applications of microfluidic platforms for cancer research: the tumor microenvironment and drug delivery systemsen_US
dc.typeThesisen_US

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