With all the improvements in cancer treatments, multidrug resistance is still the major challenge in treating cancer. Cells can develop multidrug resistance (MDR) during or after treatment, which will render the cancer cells resistant not only to the chemotherapy drug being used but also to many other structurally- and mechanically-different chemotherapeutics. In the first project, the main focus was on development of drug resistant cell lines by selection with taxol. Gene changes in the L1T2 cell line after treatment with Taxol was studied. Treatment of L1T2 cells with taxol leads to changes in the expression of ABC transporter proteins, whereas the combination of Taxol with protease inhibitors leads to increased efficacy via inhibition of P-glycoprotein (P-gp). In the second project, we showed that our innovatively-designed Au-loaded poly(lactide-co-glycolic acid) nanoparticles (GPLGA NPs) are able to cross biological barriers and deliver inside the cells without being recognized by the ABC protein transporter. (We focus specifically on P-gp-mediated drug efflux in a model of HEK cell lines.) The concentration of gold was measured using inductively-coupled plasma/mass spectrometry (ICP-MS) after 6- and 24-hour treatment of GPLGA NPs, which did not show significant increase of gold inside the cells in presence of the P-gp inhibitor valspodar. Cancer cells were treated with the GPLGA NPs for 24 hours and then irradiated 5 minutes at 1Wcm-2 using laser settings at 680 or 808 nm. Heat generation in cancer cells, after internalizing GPLGA NPs and laser irradiation, was significant irrespective of laser wavelength. The plasmomic heating response in this in vitro model can be a step closer to overcome MDR. Finally, for the third and last project represented in this dissertation, the focus was on the design and synthesis of innovative, biodegradable PLGA NPs, encapsulated with the platinum(II)-based non-organometallic/non-cyclometalated phosphorescent complex PTA = [Pt(ptp)2], a brightly phosphorescent complex (ptp = square-planar bis[3,5-bis(2-pyridyl)-1,2,4-triazolato]). Size-tunable, emission-polarized phosphorescent PTA-loaded PLGA NPs were synthesized using a single-emulsion, solvent evaporation technique. Photoluminescence characterization shows that PTA-loaded PLGA NPs exhibit strong and stable orange emission with peak maximum ~ 580 nm. The photoluminescence quantum yield (QY) of the synthesized PTA-PLGA NPs was evaluated at ~55%, which allows recording of images with a much better contrast than that with PTA in organic solvents without the PLGA (QY ~0.5% and ~0 emission polarization) or even that with typical fluorescent organic dyes like rhodamines.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc1707253 |
| Date | 08 1900 |
| Creators | Nasiri, Nooshin Mirza |
| Contributors | Omary, Mohammad A., 1969-, Gottesman, Michael M., Gryczynski, Ignacy, Simmons, Denise Perry, Marpu, Sreekar B., Slaughter, LeGrande M. |
| Publisher | University of North Texas |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | x, 101 pages : illustrations, Text |
| Rights | Public, Nasiri, Nooshin Mirza, Copyright, Copyright is held by the author, unless otherwise noted. All rights Reserved. |
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