1,721,055 research outputs found
Investigating the size effect of nanoparticles in Click Chemistry mediated cancer targeting
Get PDFSize is one of the most important properties of nanoparticles (NPs) that affects their biodistribution, accumulation and retention in the tumour tissue. The effect of NP size on tumour targeting has been studied in various contexts, with or without a targeting mechanism incorporated. Herein, we report our investigation of the size effect of NPs in Click Chemistry mediated cancer targeting. Realized by anchoring NPs onto the cell surface via metabolic glycoengineering for the cell surface placement of azido group followed by Click Chemistry mediated covalent reaction between the NP and the cell, we demonstrate that the combination effect of deeper penetration of smaller-size NP coupled with reduced clearance presumably due to the Click reaction results in its higher accumulation in the tumour tissue. Specifically, we firstly used metabolic glycoengineering to introduce azido groups to the cell surface, and then investigated the accumulation profiles of dibenzocyclooctyne conjugated nanoparticles bearing different sizes (20, 50 and 200 nm). The 20-nm silica nanoconjugates (NCs) were found to have the highest accumulation in the tumour tissue both ex vivo and in vivo. This work provides further insights into the design of nanomedicine for cancer targeting when the targeting is mediated by a non-conventional, covalent-chemistry-mediated approach.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-05-01The student, Ying Wang, accepted the attached license on 2021-04-23 at 13:04.The student, Ying Wang, submitted this Thesis for approval on 2021-04-23 at 13:07.This Thesis was approved for publication on 2021-04-28 at 15:30.DSpace SAF Submission Ingestion Package generated from Vireo submission #16443 on 2021-09-16 at 20:11:32Made available in DSpace on 2021-09-17T04:04:41Z (GMT). No. of bitstreams: 2
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Previous issue date: 2021-04-28Embargo set by: Seth Robbins for item 118687
Lift date: 2023-09-17T04:04:53Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 118687
Lift date: 2023-09-17T04:07:01Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemAuthor requested closed access (OA after 2yrs) in Vireo ETD systemLimite
Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities
Get PDFThe rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. This thesis aims to report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and to mechanistically unravel the effect of polypeptide structure on the gene delivery capability. Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities. Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent LipofectamineTM 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the top-performing materials identified also serve as promising additions to the existing systems.Item withdrawn by Laura Spradlin ([email protected]) on 2013-11-19T16:04:43Z
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University of Illinois Theses & Dissertations (ID: 1)
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Original Data
Group with Access UIUC Users [automated]
Release Date: 2016-01-16 12:19:34 UTC
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemItem marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Seth Robbins ([email protected]) on 2014-01-16T18:19:52Z
Item is restricted until 2016-01-16T18:19:34ZU of I Only Restriction Lifted for Item 46884 on 2016-01-16T11:02:06Z
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Materials and biological approach to gene delivery in human embryonic stem cells
Get PDFGene delivery is an important tool to study and manipulate human pluripotent stem cells for regenerative medicine purposes. Yet current methods of transient gene delivery are still highly inefficient. Using materials and biologically based concepts, we aim to develop new methods and protocols to enhance the efficiency of gene delivery to be useful. For the materials aspect, diblock copolymers consisting of poly(ethylene glycol)-block-poly(γ-4-(((2-(piperidin-1-yl)ethyl)amino)methyl)benzyl-L-glutamate) (PEG-b-PVBLG-8) were synthesized and evaluated for their ability to mediate gene delivery in hard-to-transfect cells like IMR-90 human fetal lung fibroblasts and human embryonic stem cells (hESCs). The PEG-b-PVBLG-8 contained a membrane-disruptive, cationic, helical polypeptide block (PVBLG-8) for complexing with DNA and a hydrophilic PEG block to improve the biocompatibility of the gene delivery vehicle. PEG-b-PVBLG-8 diblock polymers with a high degree of polymerization have a greater transfection efficiency and lower toxicity in IMR-90 cells than the commercial reagent Lipofectamine 2000. The usefulness of PEG-b-PVBLG-8 was further demonstrated via the successful transfection of hESCs without a measured loss in cell pluripotency markers. From the biological aspect, a small molecule that selectively inhibits the Rho-associated kinase inhibitor (Y-27632) was discovered that transiently alters the hESC morphology to induce spreading and reduced membrane tension. These morphological changes allowed the increase of plasmid transfection, siRNA transfection and nanoparticle uptake to increase substantially. Treating the cells with Y-27632 and passaging them as single cells, we were able to obtain a transfection efficiency of ~90% in hESCs. Cells were also able to recover after treatment back to normal pluripotent stem cell morphology and express important pluripotency markers.Item withdrawn by Mark Zulauf ([email protected]) on 2013-04-24T18:46:12Z
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University of Illinois Theses & Dissertations (ID: 1)
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Original Data
Group with Access Administrator
Release Date: 2015-05-28 14:21:22 UTC
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 44784 on 2015-05-28T10:01:46Z
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Photo-responsive degradable poly (beta-amino ester) toward non-viral gene delivery
Get PDFAmong synthetic cationic polymers, poly(beta-amino ester) (PBAE) is one of ideal candidates for non-viral gene therapy due to its desired gene delivery efficiency, biocompatibility, and biodegradability. In order to further improve the gene delivery efficiency of PBAE by facilitating the intracellular DNA dissociation, we herein report the design and development of a photo-responsive PBAE as a novel gene delivery vector which undergoes polymer degradation and promoted DNA release in response to external UV irradiation. Photo-responsive PBAE was synthesized by Michael addition of amines to (2-nitro-1,3-phenylene)bis(methylene) diacrylate (NPBMD) as a UV-responsive segment. Non-responsive PBAE (control polymer) was also synthesized when a UV-nonresponsive monomer 1,3-phenylenebis(methylene) diacrylate (PBMD) was used. By changing the monomer type and diacrylate/amine ratio, a library of UV-responsive PBAEs were obtained. Upon a screening process on the transfection efficiencies, A1-13700 was identified to be the top-performing candidate and thereafter subjected to the assessment of UV-responsive gene delivery properties. Gel permeation chromatography (GPC) and UV-vis analyses confirmed that UV irradiation triggered degradation of the responsive polymer but not the control polymer. The cationic PBAE condenses DNA into 100-nm complexes due to electrostatic interactions, and thus facilitated the cellular internalization via caveolae-mediated endocytosis. Upon UV-irradiation, particle size of the polymer/DNA complexes was augmented and DNA release was promoted as evidenced by an ethidium bromide exclusion assay and a gel retardation assay. As a result of the facilitated intracellular DNA release, UV irradiation post-transfection led to an up-to-2-fold improvement in terms of gene transfection efficiency in HeLa, COS-7, 3T3-L1 cells. Control polymers exhibited unappreciable alteration in the above assessments, further substantiating the trigger-responsive performance of PBAE towards UV light. The cytotoxicity of the polymer was slightly reduced upon UV irradiation, which suggested the degradation of cationic polymer induced cytotoxicity upon polymer degradation. This study thus provides an effective modulation over the gene transfection process using external stimuli, and helps overcome the intracellular barriers against non-viral vector mediated gene transfer.Item withdrawn by Mark Zulauf ([email protected]) on 2013-04-26T17:37:56Z
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University of Illinois Theses & Dissertations (ID: 1)
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