Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 29 for “"endosomal escape"”.
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Novel Cell Penetrating Peptides Effect Endosomal Escape and Deliver Protein Cargos into Living Cells
<p>Over the last decade a number of peptides that are rapidly internalized by mammalian cells have been discovered or designed. Cell-penetrating peptides (CPPs) are capable of mediating penetration of the plasma membrane, allowing delivery of macromolecular cargoes to the cell interior. We have …
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Towards the Design of an oligoTEA Endosomal Escape Agent: Investigations in Hydrophobicity and pKa
… and cell penetrating agents. The problem of endosomal escape in intracellular drug delivery represents an arena where this family of macromolecules may find potential use. Here, I report initial investigations into the physiochemical properties of oligoTEAs that would be relevant in tackling …
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Mechanisms of Adenovirus Membrane Permeabilization
… a non-enveloped, dsDNA virus, disrupts the endosomal membrane during cell entry is not well characterized.</p><p>Recent studies suggest that adenovirus protein VI, which is released from the interior of the capsid during cell entry, has all of the in vitro membrane lytic activity of the …
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Biochemical Investigation of the Intracellular Trafficking of Non-Viral and Hybrid Gene Therapy Vectors
… of reverse transcription, thereby estimating endosomal escape of VLP. MLV were observed to achieve reverse transcription rapidly, with more than half of infecting viruses being reverse transcribed within 8 hours. PEI:VLP were delayed approximately 4 hours (relative to viruses) in having their …
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Bioconjugate Strategies for Antisense Therapeutic Delivery to Glioblastoma Stem Cells
… inducing endocytosis, and facilitating endosomal escape. This was done within the context of glioblastoma (GBM), and specifically the glioblastoma stem cells (GSCs), an aggressive subpopulation of GBM cells that are involved in resistance, migration, and recurrence. Antisense …
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Elucidation of Design Criteria for siRNA Delivery in Mammalian Cells Using Polyethylenimine
… in vitro barriers: (1) cellular uptake, (2) endosomal escape, and (3) unpackaging of PEI/siRNA polyplexes. Chapter 2 will demonstrate that high knockdown efficiency can be achieved when appropriate amount of branched 25-kDa PEI is used despite PEI/siRNA ratio if the minimum amount of siRNA is …
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Quantitative analysis and characterization of intracellular gene delivery mechanisms
… surface association, subcellular trafficking, endosomal escape, nuclear translocation, vector unpackaging, and gene expression. Design of synthetic gene delivery vectors seeks to develop molecular systems mimicking virus-like infection behavior, including cell membrane attachment and rapid …
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Understanding barriers to efficient nucleic acid delivery with bioresponsive block copolymers
… A powerful tool for efficiently quantifying endosomal escape was developed and applied to each of the material systems described. First, a linear-dendritic poly(amido amine) -poly(ethylene glycol) (PAMAM-PEG) block copolymer system previously developed in our lab was evaluated and its ability …
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Biopolymer-Hybrid Nanomaterials for Vaccine Formulation
… were modified with three bioactive peptides, an endosomal-escape sequence (R2H2), a nuclear localisation signal (NLS) and decaarginine (R10). Although the novel materials immobilised pDNA 2x more efficiently than Arg-PDA NPs, they failed to deliver it to HEK-293 cells, most likely due to the …
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Engineering Lipid Nanoparticle-Mediated Delivery of Nucleic Acids to Lymphoid Organs and Immune Cells
… (PE) head groups likely increase endosomal escape due to their fusogenic properties. Additionally, it was found that negatively charged phospholipids drive spleen tropism. The use of a spleen selective organ targeting (SORT) formulation containing a negatively charged lipid …
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Protein engineering for cancer therapy
… dsRBD proteins deliver large amounts of siRNA to endosomal compartments in an EGFR expressing cell line, but efficient gene silencing is limited by endosomal escape. The use of a second agent that contains the cholesterol dependent cytolysin, perfringolysin 0, enhances endosomal escape of siRNA. …
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Engineering periodic short hairpin RNA delivery systems for enhanced therapeutic efficacy
… promote target cell uptake, and facilitate endosomal escape into the cytoplasm, where RNAi occurs. However, in vivo instability, low silencing efficiency, undesired toxicity, and immunogenicity remain challenges for current siRNA delivery systems, particularly as the low valency and high …
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Nanostructured gene and drug delivery systems based on molecular self-assembly
… possess modular functionalities for DNA binding, endosomal escape, steric stabilization, and tissue targeting. This part of the thesis concludes with applications of these systems to two areas of clinical interest: DNA vaccination and tumor targeted gene therapy.
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Multifunctional Chemical Cross-linkers for Drug Carriers and Molecular Probes
… surface of extracellular vesicles and quantify endosomal escape for siRNA therapeutics. Taken together, these works highlight the importance of chemical cross-linkers in the design of multifunctional bioconjugates for a variety of applications.
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Development of a Real-Time Cell Imaging Assay to Characterize the Delivery of a Cell-Penetrating Peptide Adaptor and its Associated Cargo
… system is still hindered by many issues. The endosomal entrapment problem is the main rate-limiting step for cytosolic delivery and is a result of endocytosis. To combat this issue, a new CPP, TAT-CaM, that can reach the cytosol has been developed. Conventional methods involve observing these …
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Multifunctional Nanoparticles for Cancer Imaging and Therapy
… peptides for improved cancer cell targeting and endosomal escape for delivering siRNAs. The nanoparticle displayed excellent stability and biocompatibility as evaluated by hydrodynamic size measurement over time due to the presence of a chitosan-PEG copolymer. The efficiency of gene silencing was …
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Comparative analysis of cytotoxic necrotizing factor (CNF) toxins: Compatibility of cargo with delivery vehicle and identification of amino acid residues that modulate pH-dependent cytosolic cargo delivery
… differential sensitivity of the CNF toxins to endosomal acidification impacts their cargo delivery efficiency. We found that replacing particular acidic amino acid residues from the putative insertion-trigger motif of the CNFy translocation domain with those in CNF3 promotes endosomal escape at …
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Understanding the biological barriers to Jurkat Transfection using non-viral peptides
… of cationic nanoparticles. Besides, eliminated endosomal acidification in Primary T-cells limits the endosomal escape of transfection agents based on pH sensitiveness. <br/><br/>Next, RALA and RALA-Ks variants were designed and characterised for overcoming identified barriers to T-cell …
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Structural study of lipid bicontinuous cubic phases for cellular delivery
… charged liposomes have more chance to fuse with endosomal membrane via Coulombic attraction. The increase of fusion events leads to higher delivery efficiency, however, induce higher toxicity with negatively charged cells. In this regards, new strategy or formulation of lipid based structure is …
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