Synthesis, Nanoparticle Encapsulation, and Magnetic Resonance Studies of Metal-based Anticancer Complexes PDF Download
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Author: Gregory MacNeil
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Since the discovery of cisplatin, metal complexes continue to gain interest as anticancer agents. Though a breadth of research has been conducted in this field, many pitfalls and questions remain, such as off-target activity and how exactly metal complexes exhibit their activity. In the search for novel complexes that address these issues, ruthenium and copper have become leading choices. Though a vast array of complexes employing these metals have been reported, their clinical development has often been hindered by low activity and a lack in understanding of their mechanism of action. The work in this thesis looks to address these issues in two ways: (i) by developing novel complexes and methods to breath new life into well-studied metal compounds and (ii) employ magnetic resonance spectroscopies to examine their behaviour in relevant biological environments. Chapter 2 discusses the synthesis of a novel Ru(II)-arene complex appended with a selective estrogen receptor modifier to target breast cancer. These novel complexes were subjected to several different cell assays, including the National Cancer Institute NCI-60 screen, which showed increased activity over the inactive parent ruthenium scaffolds. Chapter 3 presents 19F magnetic resonance imaging methods to develop the theranostic applications of a CF3-appended Keppler-type Ru(III) complex. It is shown that these methods can be used to spatially resolve redox and speciation events in tumour tissues, which is important to understanding their mechanism of action. Chapter 4 presents a robust method to encapsulate these CF3 appended Ru(III) anticancer complexes in polymer nanoparticles to increase their aqueous stability. Cell studies revealed an over 10-fold increase in anticancer activity over the free complexes. Chapter 5 presents and in-depth magnetic resonance study of the aqueous solution behaviour of the copper anticancer complex CasIII-ia. EPR and NMR studies were used to characterize Cu species following dissolution in complex solutions containing HSA, and in the presence of whole cells. Finally, Chapter 6 presents a novel Ru(II)-Ru(III) complex combing the unique biological activities of an organometallic Ru(II) RAPTA-type scaffold and a Ru(III) Keppler-type coordination complex. Cytotoxicity studies of the new dinuclear complex show increased activity relative to mononuclear parent compounds.
Author: Gregory MacNeil
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Since the discovery of cisplatin, metal complexes continue to gain interest as anticancer agents. Though a breadth of research has been conducted in this field, many pitfalls and questions remain, such as off-target activity and how exactly metal complexes exhibit their activity. In the search for novel complexes that address these issues, ruthenium and copper have become leading choices. Though a vast array of complexes employing these metals have been reported, their clinical development has often been hindered by low activity and a lack in understanding of their mechanism of action. The work in this thesis looks to address these issues in two ways: (i) by developing novel complexes and methods to breath new life into well-studied metal compounds and (ii) employ magnetic resonance spectroscopies to examine their behaviour in relevant biological environments. Chapter 2 discusses the synthesis of a novel Ru(II)-arene complex appended with a selective estrogen receptor modifier to target breast cancer. These novel complexes were subjected to several different cell assays, including the National Cancer Institute NCI-60 screen, which showed increased activity over the inactive parent ruthenium scaffolds. Chapter 3 presents 19F magnetic resonance imaging methods to develop the theranostic applications of a CF3-appended Keppler-type Ru(III) complex. It is shown that these methods can be used to spatially resolve redox and speciation events in tumour tissues, which is important to understanding their mechanism of action. Chapter 4 presents a robust method to encapsulate these CF3 appended Ru(III) anticancer complexes in polymer nanoparticles to increase their aqueous stability. Cell studies revealed an over 10-fold increase in anticancer activity over the free complexes. Chapter 5 presents and in-depth magnetic resonance study of the aqueous solution behaviour of the copper anticancer complex CasIII-ia. EPR and NMR studies were used to characterize Cu species following dissolution in complex solutions containing HSA, and in the presence of whole cells. Finally, Chapter 6 presents a novel Ru(II)-Ru(III) complex combing the unique biological activities of an organometallic Ru(II) RAPTA-type scaffold and a Ru(III) Keppler-type coordination complex. Cytotoxicity studies of the new dinuclear complex show increased activity relative to mononuclear parent compounds.
Author: Ravichandran Manisekaran
Publisher: Springer
ISBN: 3319676091
Category : Technology & Engineering
Languages : en
Pages : 199
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Book Description
This thesis documents the development of a multifunctional nanoparticle system to enhance the chemotherapeutic efficiency of anti-cancer drugs, and contributes to research that helps decrease the side-effects in cancer patients while simultaneously increasing their survival rates. The work begins with an introduction to nanomedicine and cancer therapy, and contains a literature review on magnetic, gold, and core-shell nanoparticles. It also covers synthesis techniques, properties, various surface modifications, and the importance of magnetic and gold nanoparticles. The author dedicates a chapter to characterization techniques, experimental setup, and cell cultivation techniques for in-vitro studies. Further chapters describe the background, characterizations, and applications of multifunctional magnetite coated gold core-shell nanoparticles, and the doping of cobalt to magnetite and manganese to magnetite nanoparticles. The important highlight of this research was the control of the size, shape, composition, and surface chemistry of nanoparticles.
Author: Nguyen Tk Thanh
Publisher: CRC Press
ISBN: 9781138051553
Category : Diagnostic imaging
Languages : en
Pages : 490
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Book Description
Controlling the size and the shape of uniform magnetic iron oxide nanoparticles for biomedical applications / Helena Gavilán, María Eugenia Fortes Brollo, Lucía Gutiérrez, Sabino Veintemillas-Verdaguer and María del Puerto Morales -- Magnetic nanochains : properties, syntheses and prospects / Irena Milosevic, Vincent Russier, Marie-Louise Saboungi, Laurence Motte -- Carbon coated magnetic metal nanoparticles for clinical applications / Martin Zeltner and Robert N. Grass -- Bio-inspired magnetic nanoparticles for biomedical applications / Changqian Cao, Yongxin Pan -- Main challenges in surface biofunctionalization of magnetic nanoparticles for in vivo targeting / Laurent Adumeau, Marie-Hélène Delville and Stéphane Mornet -- Experimental considerations for scalable magnetic nanoparticle synthesis and surface functionalization for clinical applications / Alec P. LaGrow, Maximilian O. Besenhard, Roxanne Hachani and Nguyen T.H. Kim Thanh -- Magnetic polymersomes for MRI and theranostic applications / Adeline Hannecart, Dimitri Stanicki, Luce Vander Elst, Robert N. Muller, Sophie Laurent -- Ultra-small iron oxide nanoparticles stabilized with multidentate polymers for applications in MRI / Jung Kwon (John) Oh and Marc-André Fortin -- Encapsulation and release of drugs from magnetic silica nanocomposites / Damien Mertz and Sylvie Bégin-Colin -- Current progress in magnetic separation-aided biomedical diagnosis technology / Sim Siong Leong, Swee Pin Yeap, Siew Chun Low, Rohimah Mohamud and JitKang Lim -- Magnetic separation in integrated micro analytical systems / Kazunori Hoshino -- Magnetic nanoparticles for organelle separation / Mari Takahashi & Shinya Maenosono -- Magnetic nanoparticle based biosensing / Kai Wu, Diqing Su, Yinglong Feng, and Jian-Ping Wang -- Immunotoxicity and safety considerations for iron oxide nanoparticles / Gary Hannon, Melissa Anne Tutty, Adriele Prina-Mello -- Impact of core and functionalized magnetic nanoparticles on human health / Bella B. Manshian, Uwe Himmelreich, Stefaan J. Soenen -- Magnetic nanoparticles for cancer treatment using magnetic hyperthermia / Laura Asin, Grazyna Stepien, Maria Moros, Raluca M. Fratila, and Jesus M. de la Fuente -- Nanoparticles for nanorobotic agents dedicated to cancer therapy / Mahmood Mohammadi [and 6 others] -- Smart nanoparticles and the effects in magnetic hyperthermia in vivo / Ingrid Hilger -- Non-invasive guidance scheme of magnetic nanoparticles for drug delivery in Alzheimer's disease / Ali Kafash Hoshiar [and 5 others] -- Design, fabrication, and characterization of magnetic porous PDMS as an on-demand drug delivery device / Ali Shademani, Hongbin Zhang, Mu Chiao -- Magnetic particle transport in complex media / Lamar O. Mair [and 7 others] -- Magnetic nanoparticles for neural engineering / Gerardo F. Goya, Vittoria Raffa -- Radionuclide labeling and imaging of magnetic nanoparticles / Benjamin P. Burke, Christopher Cawthorne and Stephen J. Archibald -- Red blood cells constructs to prolong the life span of iron-based magnetic resonance imaging/magnetic particle imaging contrast agents in vivo / Antonella Antonelli, Mauro Magnani -- Stimuli-regulated cancer theranostics based on magnetic nanoparticles / Yanmin Ju, Shiyan Tong, and Yanglong Hou -- Good manufacturing practices (GMP) of magnetic nanoparticles / Emre Tuereli and Nazende Guenday Tuereli
Author: WING-SHAN. LIN
Publisher:
ISBN: 9781361353929
Category :
Languages : en
Pages :
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This dissertation, "Synthesis and Biological Studies of Anti-cancer Rhodium(II, II) Carboxylates, Anti-inflammatory Silver(I) Thiourea and Microbially Fabricated Silver Nanoparticles" by Wing-shan, Lin, 林穎珊, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Discovery of cisplatin as an effective anticancer agent has stimulated the development of metal based medicine. The recent advances in research on platinum, ruthenium and gold complexes have received much attention in medicinal chemistry, and studies of other less explored metal complexes may reveal alternative mode of mechanism as novel therapeutic agents. A series of dirhodium(II, II) complexes with carboxylate and carboxamidate ligands and thiourea complexes of coinage metals have been prepared in this study. Their biological activities and mechanisms of action have been studied. Dirhodium(II, II) carboxylate complexes with variations of alkyl and benzoyl side chains were synthesized and displayed remarkable cytotoxicities to cancer cells with potency down to submicromolar level. The cytotoxicities of rhodium complexes were found to significantly correlate with the cellular uptake of the rhodium complexes. As revealed by oligonucleotide microarray and bioinformatic analysis, the mode of action of the rhodium carboxylate complexes are highly similar to that of a proteasome inhibitor. Further cellular and biochemical studies showed that rhodium carboxylate complexes induced an accumulation of ubiquitinated proteins, inhibited the proteolytic activities of purified 20S proteasome and proteasomal deubiquitinating enzyme. These results corroborate that the impairment of the ubiquitin-proteasome system is linked to the cytotoxic action of rhodium carboxylate complexes. Silver is known to be an anti-inflammatory agent for topical treatment. A silver complex of N, N''-disubstituted cyclic thiourea that is reasonably stable towards reduced glutathionewas found to potently inhibit the NF-B transcriptional activity. Treatment of cells with silver thiourea inhibited TNF-α-stimulated IκB kinase activity, IκBα phosphorylation and degradation, nuclear translocation of NF-κB p65 and eventually the stimulated gene expression of inflammatory cytokines. Suppression of IκB kinase activity was associated with modification of sensitive cysteine residues and disruption of IκB kinase assembly. These data demonstrated that the inhibitory properties of Ag+ ions on an anti-inflammatory and anti-cancer drug target could be effectively delivered via the thiourea ligand. Silver is also an antimicrobial metal, and this study was also extended to understand the silver-bacteria interaction using a silver resistant bacteria as a model. Many silver resistant bacteria often produce considerable amount of silver particles when exposed to high concentrations of silver salts but the mechanism of biosynthesis is not well understood. A silver resistant E. coli that displays active silver efflux was shown to synthesize zero-valent silver nanoparticles in the periplasmic space through reduction of silver ions under anaerobic conditions. As the microbial c-type cytochromes are known to mediate respiratory metal reduction, their role in the biosynthesis of silver nanoparticles was examined. A deletion mutant of the cytoplasmic membrane-anchored tetra-heme c-type cytochrome subunit of periplasmic nitrate reductase (NapC) showed marked reduction of accumulation of silver nanoparticles. This study identified a molecular mechanism of biosynthesis of silver nanoparticles that may have implication in bioenvironmental pro
Author: Daniel L. Fedlheim
Publisher: CRC Press
ISBN: 9780585404394
Category : Science
Languages : en
Pages : 348
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Book Description
A state-of-the-art reference, Metal Nanoparticles offers the latest research on the synthesis, characterization, and applications of nanoparticles. Following an introduction of structural, optical, electronic, and electrochemical properties of nanoparticles, the book elaborates on nanoclusters, hyper-Raleigh scattering, nanoarrays, and several applications including single electron devices, chemical sensors, biomolecule sensors, and DNA detection. The text emphasizes how size, shape, and surface chemistry affect particle performance throughout. Topics include synthesis and formation of nanoclusters, nanosphere lithography, modeling of nanoparticle optical properties, and biomolecule sensors.
Author: Zoraida Aguilar
Publisher: Newnes
ISBN: 0123850894
Category : Medical
Languages : en
Pages : 481
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Book Description
Structurally the work is demarcated into the six most popular areas of research: (1) biocompatibility of nanomaterials with living organisms in their various manifestations (2) nanobiosensors for clinical diagnostics, detecting biomolecules which are useful in the clinical diagnosis of genetic, metabolically acquired, induced or infectious disease (3) targeted drug delivery for nanomaterials in their various modifications (4) nanomedical devices and structures which are used in the development of implantable medical devices and structures such as nanorobots (5) nanopharmacology, as novel nanoparticles are increasingly engineered to diagnose conditions and recognize pathogens, identify ideal pharmaceutical agents to treat the condition or pathogens, fuel high-yield production of matched pharmaceuticals (potentially in vivo), locate, attach or enter target tissue,
Author: Alain R. Puente-Santiago
Publisher: Springer Nature
ISBN: 303055502X
Category : Science
Languages : en
Pages : 255
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Book Description
The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field.
Author: Prashant Kesharwani
Publisher: Academic Press
ISBN: 0128173319
Category : Medical
Languages : en
Pages : 434
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Book Description
Polymeric Nanoparticles as Promising Tool for Anti-cancer Therapeutics provides an understanding of polymeric compounds and their use in cancer therapies. The book begins by giving an overview of the current status, future challenges and potential utilization of polymeric nanoparticles. It then covers specific polymeric nanoparticles through contributions from world-renowned experts and researchers. Chapters examine specific polymeric nanoparticles, their development as potential targeted delivery systems, and cancer characteristics that can be targeted for therapy development. The book synthesizes current research trends in the field, thus enhancing existing knowledge of nanomedicine, drug delivery and therapeutic intervention strategies in human cancers. Users will find this to be an ideal reference for research scientists and those in the pharmaceutical and medical fields who are working to develop novel cancer therapies using nanoparticle-based delivery systems. - Explores the development of polymeric nanoparticle systems for the purpose of cancer therapy - Presents thoroughly analyzed data and results regarding the usage of polymeric nanoparticles-based platforms for the diagnosis and treatment of cancer - Highlights various cancer characteristics that can be targeted for therapeutic development using polymeric nanoparticles
Author: Vinod Kumar Yata
Publisher: Springer Nature
ISBN: 3030471209
Category : Technology & Engineering
Languages : en
Pages : 340
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Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.
Author: Brian M. Dale
Publisher: John Wiley & Sons
ISBN: 1119013038
Category : Medical
Languages : en
Pages : 246
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Book Description
This fifth edition of the most accessible introduction to MRI principles and applications from renowned teachers in the field provides an understandable yet comprehensive update. Accessible introductory guide from renowned teachers in the field Provides a concise yet thorough introduction for MRI focusing on fundamental physics, pulse sequences, and clinical applications without presenting advanced math Takes a practical approach, including up-to-date protocols, and supports technical concepts with thorough explanations and illustrations Highlights sections that are directly relevant to radiology board exams Presents new information on the latest scan techniques and applications including 3 Tesla whole body scanners, safety issues, and the nephrotoxic effects of gadolinium-based contrast media
