This 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. / Graduate / 2023-07-05
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/12039 |
| Date | 27 August 2020 |
| Creators | Papera Valente, Karolina |
| Contributors | Suleman, Afzal, Brolo, Alexandre Guimaraes |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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