School of Graduate Studies - Theses
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The School of Graduate Studies (SGS) requires doctoral and masters graduands to submit a thesis written as a required element of their degree program in electronic format.
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SGS intends to house all available digitized Doctoral and Masters theses by U of T graduate students on this site. The current collection is but a small sample of that scholarly work.
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Item Open Access 1 GHz Programmable Analog Phase Shifter for Adaptive Antennas(1997) Chua, Marcial K.Adaptive antennas are currently being considered as a means to improve spectral efficiency of wireless networks. They can be used to spatially separate different mobile user, by forming radiation pattern nulls at the interfering signals. However, the relatively high cost of adaptive antenna systems compared to non-adaptive antennas has hampered their commercial application. The purpose of this thesis is to investigate the feasibility of realizing an integrated circuit that will implement a one GHz programmable analog phase shifter, an important building block of adaptive antenna systems. This could lower the system's cost of adaptive antennas. The programmable analog phase shifter is comprised of a 900 phase shifter, a variable gain amplifier, a summer and a digital-to-analog converter. The resulting chip area is small enough to allow 16 complete phase shifter circuits to be included in a single package, thereby allowing control of an array of 16 antenna elements.Item Open Access A 1 V Floating-point Analog-to-Digital Converter for Portable Communication Devices(1998) Hayashi, TakayukiWith the growing demand for portable communications devices, power consumption has become increasingly critical in VLSI designs. In mixed-signal circuits, the push for lower supply voltage to reduce power dissipation in digital systems has forced analog systems to lower their supply voltage as well. This thesis deals with the design of a low power low voltage analog-to-digital converter (ADC) that operates from a single 1 V power supply. Two circuit techniques are utilized to enhance the performance of the converter. First, floating-point technique is employed to improve the dynamic range of the converter by providing a non-uniform quantization of the analog input. This allows the ADC to achieve a wide dynamic range without using high-resolution components. Second, current-mode technique is chosen because it offers characteristics such as good signal swings, high speed and small circuit area. The ADC was implemented using a 0.5 [mu]m, 1V CMOS process with low threshold voltage transistors. Simulation results of the core ADC cell indicate an 8-bit resolution while dissipating only 170 [mu]W. The complete floating-point ADC exhibits a dynamic range of 12 bits, a conversion time of 63 [mu]s and a power dissipation of 450 [mu]W. The total area excluding bonding pads is 1 mm 2.Item Open Access A 1 V Low-power CMOS Process(1998) Pede, Luigi DiTo reduce the size of portable telephones and other portable data communicators, and to increase the talk and use time, it is essential to reduce the power consumption of the LSI circuits that are the main components of these devices. Because the power consumption of CMOS transistors is proportional to the square of the power supply voltage, the power consumption can be dramatically reduced by cutting the power supply voltage. This will only be true however, if the threshold voltage can be scaled down proportionately to the supply voltage without increasing the standby current which otherwise increases due to subthreshold leakage. This thesis deals with the optimization of the MOSFET device structure as a means of providing 1V low power circuits in a submicron CMOS VLSI technology. Using process and device simulations, a 300 mV threshold voltage, sub 90 mV/dec subthreshold swing 1 $\mu$m LVCMOS process was developed. Due to the fact that conventional process simulations are not fully calibrated to model exact process conditions encountered experimentally, process simulations were used only as a starting point from which experimental results were used to refine the five most critical fabrication steps. High frequency and quasi-static C-V tests on n$\sp+$ and p$\sp+$ poly gates fabricated with different gate oxide thicknesses were used to establish the fabrication conditions necessary to prevent dopant penetration or polydepletion effect in 140 A gate oxide. Deep, low concentration (2 $\times$ 10$\sp{16}$ cm$\sp{-3}$) n- and p-wells with flat profiles were implemented along with suitable threshold voltage adjust implants and shallow (0.2 $\mu$m) source/drain junctions to achieve complementary long-channel devices with 300 mV threshold voltages and $<$80 mV/dec subthreshold swings. A 12 mask 16 mm$\sp2$ test chip was constructed to fully characterize the process.Item Open Access 1 V, 1.9 GHz CMOS Mixers for Wireless Applications(2001) Ye, SongThis thesis deals with the design and implementation of 1 V 1.9 GHz mixers using CMOS technology for CDMA applications. The use of CMOS allows the implementation of the mixers on the same chip with the rest of the analog and digital circuits economically while achieving high performance. The mixers topologies explored are a dual-gate mixer and a back-gate mixer. The dual-gate mixer is designed in a 0.5 um SOI process and the back-gate mixer is designed in a 0.25 um standard bulk CMOS process. Equations describing the nonlinear behavior of the CMOS dual-gate mixer are derived. The analysis yields guidelines for improving third-order intermodulation distortion of the mixer. The dual-gate mixer exhibits 1.8 dB conversion gain, -0.8 dBm IIP3 and 9.8 dB noise figure at 1.9 GHz while operating from a 1 V supply with a power consumption of 3 mW and a die area of 1.44 mm2. The back-gate mixer utilizes the inherent lateral bipolar transistor in CMOS. Device simulations were performed to analyze the behavior of the lateral bipolar transistor and extract a model for it. The characteristic of the transistor were verified through measurements. The mixer circuit only draws 1.3 mW from a 1 V supply. The measurement shows a conversion gain of 6.5 dB an IIP3 of -3.5 dBm and a noise figure of 9.7 dB at 1.9 GHz. The chip area is 1.4 mm2.Item Open Access 1,1-Hydroboration and Borane Adduct of Diphenyldiazomethane(2018-06) Tang, Connie; Stephan, Douglas W.; ChemistryThe advent of frustrated Lewis pair chemistry has demonstrated unique reactivity with a variety of small molecules. This thesis explores related chemistry with reactions of diazomethanes and highly electrophilic boranes. Diphenyldiazomethane Ph2C(N2) reacts with HB(C6F5)2 resulting in 1,1-hydroboration via a concerted reaction involving initial formation of the Lewis adduct, yielding the robust amino-borane product Ph2CN2BH(C6F5)2. Alternative synthetic routes to this product are detailed, as well as a related salt. Conversely, Ph2C(N2) reacts with B(C6F5)3 to form a highly sensitive adduct Ph2CN2B(C6F5)3. This product liberates N2 and is proposed to generate Ph2CB(C6F5)3. DFT calculations reveal that formation of this product is thermodynamically favourable from the starting compounds of carbene, N2 and borane. The isolation of this latter species opens the possibility that judicious choice of a Lewis acid and base could provide an avenue to metal-free fixation of N2.Item Open Access 1,2-DCA and VC degradation by VC-enriched and 1,2-DCA-enriched anaerobic cultures(2004) Bagard, OlivierAn anaerobic mixed microbial culture which degraded trichloroethylene to ethene was enriched on 1,2-dichoroethane (1,2-DCA). This enrichment and KB1-VC/H2, an anaerobic mixed microbial culture which was capable of sustained vinyl chloride (VC) degradation, were inocula for inhibition experiments where the interactions between 1,2-DCA, VC and chloroform (CF) were investigated. The 1,2-DCA culture degraded 1,2-DCA first within 10 days and eventually degraded VC after a sixty-day lag. The VC culture could degrade VC and 1,2-DCA simultaneously within ten to forty days. In the 1,2-DCA culture, 1,2-DCA was likely degraded by an organism suspected to be Syntrophus-KB1. In the VC culture, 1,2-DCA was degraded by Dehalococcoides-KB1 or by the unidentified organism. VC was a competitive inhibitor of 1,2-DCA degradation with an inhibition constant of 55muM. CF was a non-competitive inhibitor of 1,2-DCA and VC degradations: inhibition constants were equal to 10muM for 1,2-DCA degradation and 1.6muM for VC degradation.Item Open Access A 1-1-1-1 MASH Delta-Sigma ADC using Dynamic Comparator-based OTAs(2013-01-08) Yamamoto, Kentaro ; Anthony, Chan Carusone ; Electrical and Computer EngineeringLow intrinsic transistor gain in nanometer CMOS technologies imposes implementation difficulties of switched-capacitor (SC) circuits based on a conventional OTA used in delta-sigma ADCs. Zero-crossing-based circuits (ZCBCs) have been proposed as replacements for conventional OTAs in SC circuits, but the efficiency of existing ZCBC-based delta-sigma ADCs trails that of state-of-art conventional delta-sigma ADCs. The dynamic comparator-based OTA (DCBOTA) is a novel circuit block that performs an equivalent operation of a conventional OTA in a SC circuit by repeatedly detecting the input (Vg) sign and applying output current pulses to move Vg toward zero. The current pulse amplitude, set to the maximum at the beginning of a charge transfer phase, is decremented each time Vg crosses zero. Once Vg crosses zero at the minimum current pulse amplitude, the operation above ceases. The discrete-time nature of Vg comparison and current pulse injection in the DCBOTA allows use of a dynamic regenerative comparator, which is fast and scaling friendly, instead of the slow scaling-unfriendly open-loop zero-crossing detector used in ZCBCs. A small final Vg step size is required for high settling accuracy, but it can result in a long settling time. Analysis reveals that the DCBOTA settling time is minimized with a current pulse scaling factor of 3.59 for any final Vg step size. The comparator and switch noise affects the settling DCBOTA settling accuracy. The relationship between the minimum Vg step size, comparator noise, and switch noise for a given input-referred noise is shown. The DCBOTA consists of a dynamic regenerative comparator, control logic, and current pulse driver. The comparator evaluates the Vg sign when enabled by the control logic. The control logic enables and resets the comparator, and controls the current pulse amplitude. The current pulse driver applies either a positive or negative output current pulse when triggered by the comparator output. A 1-1-1-1 MASH delta-sigma ADC using DCBOTAs fabricated in a 65-nm CMOS technology achieved 70.4 dB of peak SNDR over a 2.5-MHz bandwidth dissipating 3.89 mW of power from a 1.2-V supply. Measurements show linear ADC power scaling over sampling frequencies provided by the dynamic operation of the DCBOTAs.Item Open Access A 1-V, CMOS on SOI, 1.9-GHz CDMA Low Noise Amplifier(2000) Jin, HengThis thesis deals with the design and implementation of a 1V, 1.9GHZ low noise amplifier (LNA) using a 0.5[mu]m CMOS on SOI technology with 3 levels of metal. The amplifier is optimized for CDMA applications operating in the 1.93-1.99GHz band. The inductive degeneration topology used in the LNA implementation provides low noise and low power dissipation. The use of CMOS on SOI technology may lead to an optimum single chip implementation of both the analog and digital building blocks of a 1.9GHz transceiver operating from a 1V supply. Such an implementation offers reduced cost and improved reliability. The LNA consists of two amplifying stages with on-chip inductors and capacitors. At 1.96GHz, the amplifier has a 1.9dB noise figure, a 14dB gain and a 3dBm IIP3. It also exhibits 17.4dB input and 28.3dB output return losses respectively in a 50[Omega] system without external matching networks. The circuit draws 10.6mW from a 1V supply and the chip area is 1.1 x 2.4 mm2.Item Open Access 1. Synthetic applications of aziridines: New approaches to the development of asymmetric catalysts. 2. Studies of new reactivity fo p-tolylsulfinayl amides towards olefins(2003) Krasnova, Larissa BThe new N,N-ligands have been synthesized. It was shown that Cu(I) coordinates to the ligands. Enantiomerically pure forms of this ligand were obtained and applied to the cyclopropanation reaction, where the copper catalyst revealed unexpectedly high diastereoselectivity in comparison with the ruthenium catalyst. Observed diastereoselectivities are superior to the known copper catalyzed cyclopropanation. New reactivity of the sulfinyl amide was discovered. Reaction between alkenes and sulfinyl amides in the presence of POCl3 was found to proceed with the formation of β-chlorosulfides. Optimized reaction conditions were applied to a wide range of substrates. In the absence of nucleophile under Lewis acid conditions p-tolylsulfinyl amide reacted with α-methylstyrene with the formation of allylsulfoxide. This chemistry provides a reasonable alternative to currently used oxidative methods of sulfoxides synthesis.Item Open Access A 1.25GS/s 8-bit Time-interleaved C-2C SAR ADC for Wireline Receiver Applications(2013-12-11) Wang, Qiwei ; Carusone, Anthony Chan ; Electrical and Computer EngineeringMany wireline communication systems are moving toward a digital based architecture for the receiver that requires a front-end high-speed ADC. This thesis proposes a two-level time-interleaving topology for realizing such an ADC, comprising front-end time-interleaved sub-rate track-and-holds each followed by a sub-ADC which is further time-interleaved to a slower clock frequency. The design, implementation and measurement of the 1.25GS/s sub-ADC fabricated in 65nm CMOS technology is presented. The SAR architecture is chosen for its low power and digital friendly nature along with an unconventional C-2C capacitive DAC implementation for higher bandwidth. The time-interleaved C-2C SAR ADC runs with a 1.0V supply, and it has a full input range of 1.0V\subscript{pp} differential, while consuming 34mW. The SNDR is 39.4dB at low frequency and the FOM is 360fJ/conv-step and 428fJ/conv-step at low and Nyquist input frequencies respectively. The SNDR is 34dB at 4GHz input frequency, which is more than 6 times the Nyquist frequency.Item Open Access A 1.8V 2nd-Order [sigma delta] Modulator(1999) Yang, WeiLow-voltage, low-power analog-to-digital converters provide a critical interface in portable mixed-signal electronic systems. The robustness and tolerance of the sigma-delta modulator technique over other data-converter techniques make it an ideal choice in applications where low voltage and high-dynamic range are a must. This thesis deals with the design and implementation of a low-voltage, low-power 2nd-order sigma-delta modulator with a single 1.8 V power supply using conventional threshold voltage transistors. All the circuit blocks are integrated on one chip, and the input common-mode voltage is set at mid-rail, resulting in low power dissipation, minimum off-chip components, and high efficiency, flexibility and compatibility. The design is useful for voice applications in personal communications systems supplied by two nickel-cadmium or alkaline batteries. The modulator consists of four circuit blocks: the biasing, the operational amplifier, the comparator-latch, and the four-phase clock generator. A high DC gain, large output swing operational amplifier with a low-voltage power supply was implemented using a fully-differential folded-cascode input stage followed by a common-source output stage, combined with a switched-capacitor common-mode feedback circuit. Based on fully-differential switched-capacitor techniques, the modulator was implemented using a 3.3 V, double-poly, 0.35[mu]m CMOS process. The modulator exhibits a 15-bit dynamic range for a 7 kHz bandwidth, and a 14-bit dynamic range for a 20 kHz bandwidth at an oversampling frequency of 2.56 MHz. The complete 2nd-order modulator has a power dissipation of 0.99 mW, and occupies 0.31 mm2 of the area excluding bonding pads.Item Open Access A 10 bit, 50MS/s, Low-Power Pipelined A/D Converter for Cable Modem Applications(2001) Hamedi-Hagh, SotoudehCable modems have been recently developed for high speed, bidirectional communication over the broadband hybrid fiber-coaxial network. Such modems use mixed-mode circuits to achieve high performance interactive multimedia communications. The digital back-end circuits in the cable modem are implemented in a submicron CMOS process for low power dissipation and high speed of operation. To realize low cost and single chip modems, the analog front-end circuits must be implemented together with the digital circuits on the same chip. A crucial block in the cable modem is the high performance A/D converter which operates in the in-band downstream receiver and links the analog front-end to the digital back-end circuitry. This thesis deals with the design of a pipelined A/D converter realized using a one bit per stage pipelined architecture for use in cable modems. The A/D converter includes the input track-and-hold circuit, clock timing generator, digital synchronization block and the pipelined stages. The pipelined A/D converter is implemented in a 0.25-[mu]m, 2.5-3.3V CMOS process, with single layer of polysilicon and 5 levels of metallization and uses an area of 3.2mm2. The prototype exhibits a 10 bits resolution at 50MSample/s and 57dB SNDR while dissipating 65mW from a 2.5V supply voltage. The DNL and the INL are -0.5LSB and 0.95LSB respectively and the area of the core excluding pads is 1.2mm2. Compared to the best previous design with the same resolution and sampling speed, this design achieves the same dynamic range at lower supply voltage, lower power dissipation and with a smaller core area.Item Open Access A 100-200 MHz Ultrasound Biomicroscope(1999) Knapik, Donald AndrewClinical ultrasound imaging systems capable of producing real-time, economical, cross sectional images of soft tissue are in widespread use. The resolution of these system is not sufficient for certain specialised applications. A 100-200 MHz ultrasound system providing resolution from 14-35 [mu]m has been produced. Transducers were custom built using a novel design. The properties of two transducers, one at 100 MHz and the other at 200 MHz, have been characterised and they compare well with theoretical values. A minimum insertion loss of 18 dB has been measured. Real-time images have been obtained at 100 MHz. At 200 MHz higher quality images were created with a slower, zone focus scan. Adequate contrast and penetration are shown in images of ocular tissue, superficial skin and a coronary artery. These examples show the potential for clinical utility of this system in assessing superficial conditions such as corneal disease, melanoma and atherosclerosis.Item Open Access 111In-labeled Nimotuzumab Modified with Nuclear Localization Sequences (NLS): An Auger Electron-emitting Radiotherapeutic Agent for EGFR-overexpressing and Trastuzumab-resistant Breast Cancer(2011-08-24) Fasih, Aisha ; Reilly, Raymond Matthew ; Pharmaceutical SciencesObjective: The cytotoxic property of anti-EGFR-1 monoclonal-antibody nimotuzumab modified with nuclear localization sequence and radiolabeled with 111In was evaluated in trastuzumab-resistant breast cancer cells. Methods: 111In-nimotuzumab-NLS was constructed and its immunoreactivity was determined. Cellular and nuclear uptake was evaluated by cell fractionation. Finally, the cytotoxicity of conjugates (111In-nimotuzumab/111In-nimotuzumab-NLS) was studied by clonogenic assays. Results: The immunoreactivity of 111In-nimotuzumab-NLS was conserved. 111In-nimotuzumab-NLS exhibited 2-fold higher nuclear translocation as compared to 111In-nimotuzumab in MDA-MB-468 cells. Nuclear importation of 111In-nimotuzumab-NLS in MDA-MB-468 cells was 4-fold and 6-fold higher than moderate and low EGFR expressing cell lines, respectively. Clonogenic survival (CS) for MDA-MB-468 cells showed 111In-nimotuzumab-NLS to be 10-folds and 60-folds more potent than 111In-nimotuzumab and nimotuzumab, respectively. Moderate killing for TrR1 and MDA-MB-231 was observed. 111In-hEGF showed significantly higher cytotoxicity and 2-fold higher γ-H2AX foci integrated density/nuclear-area as compared to 111In-nimotuzumab-NLS. Preserved selectivity of 111In-nimotuzumab-NLS makes it an excellent drug for treating cancers.Item Open Access 13-deoxytetrodecamycin and Thamamycin: Two Promising Tetrodecamycin Antibiotics(2021-09) Lefebvre, Maxime; Nodwell, Justin JN; BiochemistryAntibiotic-resistant bacteria pose a serious threat to modern medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most alarming pathogens due to its prevalence in hospitals and the community and the emergence of multi-drug resistant isolates. 13-deoxytetrodecamycin (13-dTDM) and thamamycin (THM) are novel, related members of the tetrodecamycin antibiotic class that are bioactive against MRSA. Presently, their targets and mode of action are unknown although their structural novelty and potency against drug-resistant bacteria makes them very attractive subjects for research. The aim of this thesis was to increase the yield of 13-dTDM and THM in order to elucidate their molecular target and mode of action. Utilizing a ‘ribosome engineering’ approach, I have successfully increased the yield of THM. I also demonstrate that 13-dTDM and THM are bactericidal and do not target the lipid II cycle of cell wall biosynthesis. Lastly, preliminary data suggests possible targeting of the folate pathway by THM.Item Open Access A 131-Year High-Resolution Record of Coccolith Assemblages in Laminated Sediments from the Arabian Sea(2010-09-03) Akrami, Maryam; Bollmann, Jorg; GeologyThis study looked at a 131-year high-resolution record of coccolith assemblages in laminated sediments from the Arabian Sea. The SO90-39KG core obtained from the northeastern Arabian Sea was sampled at an annual resolution for the period of 1861-1993 A.D. Analyses of Scanning Electron Microscope (SEM) images of these samples revealed a declining trend in the relative abundances of the upper to mid photic zones coccolithophore species and an increasing trend in the relative abundances of the lower photic zone coccolithophore species over the 20th century. These trends could be the result of a reduction in paleoproductivity caused by the deepening of the nutricline and the thermocline due to a warming climate. The 1883 A.D. Krakatau eruption was also evident in the results as decreased paleoproductivity. Similarities between the observed trends and monsoon precipitation as well as sunspot cycle records were also observed. No particular similarity with El-Nino Southern Oscillation (ENSO) record could be detected. Caution should be observed regarding the correlation of the results obtained here to past climatic and geologic events.Item Open Access 13C PEG as an In Vivo Macromolecular Probe for MRI and Biophysical Studies of Detergent-Peptide and Detergent-Detergent Interactions using NMR(2015-06) Alvares, Rohan; Prosser, Robert S; Macdonald, Peter M; ChemistryIn the first part of this thesis, a new platform technology is demonstrated for the direct in vivo observation and quantification of macromolecular constituents, such as proteins and drug delivery systems, using 1H MRI. To overcome sensitivity challenges, a 28 kDa non-immunogenic tag is employed, consisting of 13C-enriched polyethylene glycol (PEG), whose spectroscopically equivalent 1H nuclei provide a signal amplification of 2500. Passing the 1H PEG signal through the directly coupled 13C nuclei enables the removal of background water and fat signal. Imaging capabilities are demonstrated by monitoring the real-time clearance of PEG and pegylated albumin in the hind leg of a mouse. Improvements to the initial imaging methodology are subsequently proposed, which increase the sensitivity and extend the imaging capabilities to abdominal and cranial regions. Ex vivo detection of pegylated constituents is also possible using NMR spectroscopy. Using blood as a sample biological fluid, clearance profiles of both unlabeled and 13C labelled PEG, as well as a pegylated protein were determined in rats. The second part of this thesis describes biophysical interactions of detergents with either peptides or other detergent molecules. Firstly, the effects induced by a single polar substitution on the structure and topology of model α-helical transmembrane segments were investigated. Upon substitution of a central isoleucine for an asparagine, diffusion NMR measurements revealed that the asparagine-containing peptide bound ~ 20% less detergent. Secondly, NMR was used to investigate the micellization process. A rapid method to determine thermodynamic and volumetric parameters, which relies on a single subtle change in the 1H chemical shift, was developed. The thermodynamic quantities were then related to spectroscopic studies of topology and micelle structure.Item Open Access 15-Hydroxyprostaglandin dehydrogenase protein expression in human preterm fetal membranes(2006) Rizek, Rose MarieProstaglandins are important in the onset of labour. 15-hydroxyprostaglandin dehydrogenase (PGDH) metabolizes prostaglandins and is downregulated in preterm labour with and without infection. We detected a predominant 29kDa and 55kDa form of immunoreactive-PGDH in preterm chorion and amnion, respectively. 29kDa PGDH expression was unchanged with preterm premature rupture of membranes (PPROM), gestational age, glucocorticoid administration or subclinical inflammation. However, in amnion, 55kDa PGDH increased with PPROM atItem Open Access 157-nm radiation induced bragg gratings in silica optical waveguides(2003) Chen, Eddy GThis thesis reports the first detailed study of Bragg grating writing using 157-nm radiation. The 7.9-eV photon from the 157-nm laser is attractive for inducing strong index changes in germanosilicate and fused silica. Fiber Bragg gratings were written in standard telecom fiber (SMF-28), with index modulation of ∼1.7 × 10−4 in hydrogen-free SMF-28. The gratings have good long-term stability, and sidelobe suppression of 17 dB without apodization. The index modulation improves to ∼6 × 10−4 and Δn∼1.8 × 10−3 in hydrogen-loaded SMF-28. Bragg gratings were fabricated in pure fused silica holey fiber, yielding Δn∼1.4 × 10−3 at 90 kJ/cm2 fluence exposure, and offered good cladding mode suppression. Bragg gratings were also written within silica-on-silicon planar waveguides and buried waveguides in fused silica blocks. The results demonstrate an alternate laser source for writing fiber Bragg gratings not requiring photosensitivity enhancement in germanosilicate waveguides, and is practical for writing gratings in pure fused silica holey fiber.Item Open Access 177Lu-labeled Gold Nanoparticles for Radiation Therapy of Locally Advanced Breast Cancer(2016-06) Yook, Simmyung; Reilly, Raymond M; Pharmaceutical SciencesLocally advanced breast cancer (LABC) occurs in about 10-15% of patients diagnosed with breast cancer (BC) and 30% of these patients have triple negative breast cancer (TNBC) that are often epidermal growth factor receptor (EGFR)-positive. The goal of the proposed research was design and evaluate preclinically a novel radiation nanomedicine for LABC composed of EGFR-targeted gold nanoparticles (AuNP) by covalently conjugating panitumumab and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexing 177Lu incorporated into a metal-chelating polymer (MCP) (177Lu-T-AuNP) which could be used as a neoadjuvant treatment to improve the outcome of patients with LABC. 177Lu-T-AuNP were efficiently internalized by EGFR-positive BC cells and were significantly more effective than 177Lu-labeled and non-targeted (NT)-AuNP for killing these cells. For radiation treatment of EGFR-positive tumours, both 177Lu-T-AuNP and 177Lu-NT-AuNP were intratumourally (i.t.) injected into athymic mice with MDA-MB-468 BC xenografts for comparison. Biodistribution studies showed that 177Lu-T-AuNPs exhibited 2-fold higher tumour retention than 177Lu-NT-AuNPs following i.t. injection at 48 h p.i. Both forms of radiolabeled AuNP were highly effective for inhibiting tumour growth without normal organ toxicity due to local tumour retention of both form of AuNP. To minimize the displacement of 177Lu-labeled MCP from AuNP, polyethylene glycol (PEG) ligands presenting a disulfide [177Lu-DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a lipoic acid (LA) [177Lu-DOTA-PEG-lipoic acid (LA)] or multi-LA [PEG-pGlu(177Lu-DOTA)8-LA4] for multivalent binding were synthesized and the stability of MCP-AuNP complexes determined. In vitro challenge study with thiol-containing molecules or human plasma, PEG-pGlu(DOTA)8-LA4-AuNP were most stable. In whole body elimination study, elimination of radioactivity due to displacement of 177Lu-MCP from AuNP in mice injected with 177Lu-DOTA-PEG-OPSS-AuNP was more rapid, indicating that 177Lu-DOTA-PEG-OPSS-AuNP was less stable than two other forms of 177Lu-MCP-AuNP. Since MCP presenting a terminal multi-LA group provides the greatest stability, this conjugation chemistry is the most promising for construction of 177Lu-labeled and antibody-targeted AuNP for neoadjuvant treatment of LABC.