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dc.contributor.advisorMiller, Lawrence Wen_US
dc.contributor.authorRivera Vera, Claudia Ivetteen_US
dc.date.accessioned2018-02-08T21:31:42Z
dc.date.available2018-02-08T21:31:42Z
dc.date.created2017-12en_US
dc.date.issued2017-12-06en_US
dc.date.submittedDecember 2017en_US
dc.identifier.urihttp://hdl.handle.net/10027/22251
dc.description.abstractSemiconductor nanocrystals or quantum dots (QDs) possess exceptional optical and physicochemical properties, for instance, their brightness and long fluorescence lifetimes, which makes them valuable for live-cell imaging. Due to their large size, QDs do not cross cell membranes passively, fortunately, this issue can be addressed by coating QDs with cell penetrating peptides (CPPs) such as the TAT sequence or polyarginine as it has been reported by several studies from different labs. We could intracellularly deliver CPP coated red and green emitting QDs, however, as many others have shown, we also found that endocytosis was the major mechanism of intracellular uptake in HeLa cells, and consequently, QDs remained trapped inside the endosomes without being able to reach the cytosol. In this thesis, I designed and synthesized a few peptides with purported potential endosomal escape activity. These peptides were conjugated to the QD surface, and we showed that a peptide derived from Aurein 1.2 and a polyamine derivative significantly enhanced the endosomal escape of our QD bioconjugates in live cell studies. Further, we developed a FRET (Forster resonance energy transfer)-based method to quantify the endosomal escape triggered by the Aurein 1.2, polyamine, and palmitoyl peptides respectively, along with a small protein (HA2) derived from the influenza virus. Our FRET sensor system is comprised of a QD (as the FRET donor) linked to a rhodamine labeled peptide (as the FRET acceptor) through a disulfide bond, and thus, rendering a ratiometric FRET system that measures the extent of endosomal escape by the change in red/green signal upon disulfide bond cleavage by cytosolic glutathione. Collectively, our qualitative and quantitative microscopy studies indicate that both, Aurein 1.2, as well as a polyamine peptide I designed from scratch, do enhance endosomal escape of QDs in live-cell studies. I also performed more than 95% of the synthetic work displayed in this thesis.en_US
dc.format.mimetypeapplication/pdfen_US
dc.subjectQuantum dotsen_US
dc.subjectendosomal escape abilityen_US
dc.subjectrhodamineen_US
dc.subjectFRETen_US
dc.subjectCPPen_US
dc.subjectHA2en_US
dc.subjectAurein 1.2en_US
dc.subjectHAfp23en_US
dc.subjectPalmitoylen_US
dc.subjectSPPSen_US
dc.subjectglutathioneen_US
dc.subjectendosomolyticen_US
dc.subjectimagingen_US
dc.subjectconfocal microscopyen_US
dc.subjectTATen_US
dc.subjectTAT-HA2en_US
dc.subjectpolyarginineen_US
dc.subjectspermineen_US
dc.subjectpolyamineen_US
dc.subjectratiometric FRETen_US
dc.subjectFRET donoren_US
dc.subjectFRET acceptoren_US
dc.subjectdark quencheren_US
dc.subjectBHQ-2en_US
dc.subjectQSY-7en_US
dc.subjectQSY-21en_US
dc.subjectfacilitated delivery of QDsen_US
dc.subjectsynthesisen_US
dc.subjectMALDIen_US
dc.titlePeptide-Based Strategies of Delivering Semiconductor Nanocrystals into Living Cellsen_US
dc.typeThesisen_US
thesis.degree.departmentChemistryen_US
thesis.degree.grantorUniversity of Illinois at Chicagoen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhD, Doctor of Philosophyen_US
dc.contributor.committeeMemberWardrop, Duncanen_US
dc.contributor.committeeMemberMin, Jung-Hyunen_US
dc.contributor.committeeMemberMohr, Justinen_US
dc.contributor.committeeMemberPerez-Salas, Ursulaen_US
dc.type.materialtexten_US
dc.contributor.chairMiller, Lawrence Wen_US


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