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<p class="MsoNormal"><span style="font-family:"Arial",sans-serif;color:black"><img width="600" height="171" style="width:6.25in;height:1.7812in" id="_x0000_i1026" src="https://www.egr.uh.edu/sites/www.egr.uh.edu/files/enews/2022/images/dissertation1.png" alt="Dissertation Defense Announcement at the Cullen College of Engineering"><o:p></o:p></span></p>
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<strong><span style="font-size:18.0pt;font-family:"Calibri",sans-serif;color:#C8102E">Design and Development of Patchy Liposomes as Delivery Nanocarriers with Enhanced Cellular Internalization</span></strong><span style="font-size:18.0pt;color:#C8102E"><o:p></o:p></span></p>
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<b><span style="font-size:13.5pt">Yifei Wang</span></b><span style="font-size:13.5pt"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif">April 25, 2023; 10:00 AM - 12:00 PM (CST)<br>
Location: L2D2<br>
Zoom: <a href="https://urldefense.com/v3/__https:/uh-edu-cougarnet.zoom.us/j/95368628013__;!!LkSTlj0I!Ac5I5xmAZDNFVQw074Tg11nSch-0PckClg2-VNlclDtdpcC_F0AbG5rC_7A9uXKYtd7R1Ay8aYs5a83ebk_pppaeEw4$">https://uh-edu-cougarnet.zoom.us/j/95368628013</a><o:p></o:p></span></p>
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<strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif">Committee Chair:</span></strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif"><br>
Sheereen Majd, Ph.D.<o:p></o:p></span></p>
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<strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif">Committee Members:</span></strong><span style="font-size:10.5pt;font-family:"Arial",sans-serif"><br>
Mohammad Reza Abidian, Ph.D. | Tianfu Wu, Ph.D. | Diana Shu-Lian Chow, Ph.D. | Guangwei Du, Ph.D.<o:p></o:p></span></p>
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<strong><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E">Abstract</span></strong><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E"><o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif"> Nanoliposomes are one of the most commonly used delivery nanocarriers due to their biocompatibility, biodegradability, and low toxicity. To achieve high levels of cellular uptake, liposomes
often require large doses of fusion-promoting molecules or targeting ligands that can lead to undesired side effects, including toxicity and immunogenicity. To address this challenge, this project aims to utilize the biological process of membrane phase-separation
to design and develop liposomes that can offer highly efficient cellular internalization with minimal toxicity. <o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif"> First part of this dissertation combines experimental and computational tools to investigate the phase behavior of multi-component lipid membranes. The experimental studies focused on
studying phase-separation on micron-sized liposomes of various compositions using fluorescence microscopy. In collaboration with mathematicians, two continuum phase-field models were then developed to simulate the phase-separation examined in experiments.
Great agreement between experiments and simulations validated the computational models and demonstrated their potential use for the design of phase-separating and patchy liposomes. <o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif"> Second part of this dissertation explores the use of phase-separation to create highly fusogenic liposomal nanocarriers with minimal toxicity. The impact of charged lipids on membrane’s
phase behavior was first investigated in multi-component micron-sized liposomes. The findings of this work were then applied towards designing fusogenitic liposomes with cationic patches that showed enhanced fusogenicity compared to their homogenous counterparts.
This work demonstrated that phase-separation can be applied to enhance the performance of cationic delivery liposomes.<o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif"> The last part of this dissertation seeks to use phase-separation to enhance targeting selectivity of ligand-conjugated liposomes. Using biotin-streptavidin, as a model system, biotinylated
liposomes were designed to respond to acidic pH in tumor environment to undergo phase-separation and present their ligands in highly-dense patches for enhanced binding. Current studies focus on applying this concept to achieve enhanced cell uptake. <o:p></o:p></span></p>
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<span style="font-size:10.5pt;font-family:"Arial",sans-serif"> This dissertation provides an insight into the use of phase-separation to control the functionality of lipid membranes and it hence, offers new possibilities to overcome the shortcomings
of current liposomal nanocarriers.<o:p></o:p></span></p>
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<p class="MsoNormal"><span style="font-family:"Arial",sans-serif;color:black"><img border="0" width="600" height="82" style="width:6.25in;height:.8541in" id="_x0000_i1025" src="https://www.egr.uh.edu/sites/www.egr.uh.edu/files/enews/2022/images/dissertation2.png" alt="Engineered For What's Next"><o:p></o:p></span></p>
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