The Development of Mononuclear Platinum Hybrid Biomaterials for Antigene Therapeutic Application PDF Download
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Author: Joseph Hennessy
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Since the serendipitous discovery of cisplatin by Rosenberg platinum agents based on the traditional cis chemotype are still the cornerstone of platinum therapeutic application with cisplatin, carboplatin and oxaliplatin as the only agents approved globally for use. Past research has focused mainly on elucidating the mechanistic action of these traditional Pt(II) agents with great success and streamed into efforts centred on trying to reduce the potent toxic side-effects such as nephrotoxicity, ototoxicity and poor target selectivity. Classes of platinum complexes such as trans-substituted platinum(II) agents, platinum(IV) prodrugs, polynuclear platinum(II) complexes and in particular, platinum(II)-DNA hybrids produced for an antigene strategy, have all observed a significant renewal of interest in recent years. This thesis focuses on the development of a library of platinum(II)-triplex forming oligonucleotide hybrids that possess targeted antigene applications. Firstly, the synthesis of azide-functionalised ligands and their complexation with platinum to form azide-functionalised cis-platinum(II) complexes is reported. Thereafter, the design and synthesis of triplex forming oligonucleotides (TFOs) is reported and followed by the utilisation of the copper-catalysed and strain promoted alkyneazide cycloaddition or 'click chemistry' to generate gene-directed cis-platinum(II)TFO hybrids. The work reported represents the first example of click chemistry strategies being employed to afford cis-platinum(II)-TFO constructs designed this way. DNA interaction studies identified that the azide-functionalised platinum(II) complexes retain activity against dsDNA targets. The cis-platinum(II)-TFO constructs demonstrated sequence specific triplex recognition with no off-target effects observed in the presence of purine rich sequences. However, in general the crosslink formation on target genes of interest by the platinum(II) ion destabilises triplex formation. The introduction of TO - a known intercalating fluorophore - can remediate this destabilisation and this work demonstrates how TO-modified cis-Pt(II)-TFOs retain their targeting abilities with enhanced stabilising characteristics. Finally, TFO constructs containing a novel alkyne-amine nucleobase were developed and investigated for their ability to incorporate TO and Pt(II). This strategy was developed to enhance site-specific metal ion-DNA target interactions whereby the proximity of the complex to the DNA interface was enhanced under the guidance of the neighbouring TO intercalator. The conjugation of Cu(II)-phenanthrene-type scaffolds with alkyne-modifed TFOs to generate novel Cu(II)-AMN-TFOs has afforded unique stabilising properties and represent an innovative class of gene-targeted system.
Author: Joseph Hennessy
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Since the serendipitous discovery of cisplatin by Rosenberg platinum agents based on the traditional cis chemotype are still the cornerstone of platinum therapeutic application with cisplatin, carboplatin and oxaliplatin as the only agents approved globally for use. Past research has focused mainly on elucidating the mechanistic action of these traditional Pt(II) agents with great success and streamed into efforts centred on trying to reduce the potent toxic side-effects such as nephrotoxicity, ototoxicity and poor target selectivity. Classes of platinum complexes such as trans-substituted platinum(II) agents, platinum(IV) prodrugs, polynuclear platinum(II) complexes and in particular, platinum(II)-DNA hybrids produced for an antigene strategy, have all observed a significant renewal of interest in recent years. This thesis focuses on the development of a library of platinum(II)-triplex forming oligonucleotide hybrids that possess targeted antigene applications. Firstly, the synthesis of azide-functionalised ligands and their complexation with platinum to form azide-functionalised cis-platinum(II) complexes is reported. Thereafter, the design and synthesis of triplex forming oligonucleotides (TFOs) is reported and followed by the utilisation of the copper-catalysed and strain promoted alkyneazide cycloaddition or 'click chemistry' to generate gene-directed cis-platinum(II)TFO hybrids. The work reported represents the first example of click chemistry strategies being employed to afford cis-platinum(II)-TFO constructs designed this way. DNA interaction studies identified that the azide-functionalised platinum(II) complexes retain activity against dsDNA targets. The cis-platinum(II)-TFO constructs demonstrated sequence specific triplex recognition with no off-target effects observed in the presence of purine rich sequences. However, in general the crosslink formation on target genes of interest by the platinum(II) ion destabilises triplex formation. The introduction of TO - a known intercalating fluorophore - can remediate this destabilisation and this work demonstrates how TO-modified cis-Pt(II)-TFOs retain their targeting abilities with enhanced stabilising characteristics. Finally, TFO constructs containing a novel alkyne-amine nucleobase were developed and investigated for their ability to incorporate TO and Pt(II). This strategy was developed to enhance site-specific metal ion-DNA target interactions whereby the proximity of the complex to the DNA interface was enhanced under the guidance of the neighbouring TO intercalator. The conjugation of Cu(II)-phenanthrene-type scaffolds with alkyne-modifed TFOs to generate novel Cu(II)-AMN-TFOs has afforded unique stabilising properties and represent an innovative class of gene-targeted system.
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: National Research Council
Publisher: National Academies Press
ISBN: 0309173051
Category : Medical
Languages : en
Pages : 74
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Book Description
The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) on April 23, 1997, to prohibit the use of animals in the production of mAb. On September 18, 1997, NIH declined to prohibit the use of mice in mAb production, stating that "the ascites method of mAb production is scientifically appropriate for some research projects and cannot be replaced." On March 26, 1998, AAVS submitted a second petition, stating that "NIH failed to provide valid scientific reasons for not supporting a proposed ban." The office of the NIH director asked the National Research Council to conduct a study of methods of producing mAb. In response to that request, the Research Council appointed the Committee on Methods of Producing Monoclonal Antibodies, to act on behalf of the Institute for Laboratory Animal Research of the Commission on Life Sciences, to conduct the study. The 11 expert members of the committee had extensive experience in biomedical research, laboratory animal medicine, animal welfare, pain research, and patient advocacy (Appendix B). The committee was asked to determine whether there was a scientific necessity for the mouse ascites method; if so, whether the method caused pain or distress; and, if so, what could be done to minimize the pain or distress. The committee was also asked to comment on available in vitro methods; to suggest what acceptable scientific rationale, if any, there was for using the mouse ascites method; and to identify regulatory requirements for the continued use of the mouse ascites method. The committee held an open data-gathering meeting during which its members summarized data bearing on those questions. A 1-day workshop (Appendix A) was attended by 34 participants, 14 of whom made formal presentations. A second meeting was held to finalize the report. The present report was written on the basis of information in the literature and information presented at the meeting and the workshop.
Author: Abbass A. Hashim
Publisher: BoD – Books on Demand
ISBN: 9535106155
Category : Science
Languages : en
Pages : 556
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Book Description
Nanoparticle is a general challenge for today's technology and the near future observations of science. Nanoparticles cover mostly all types of sciences and manufacturing technologies. The properties of this particle are flying over today scientific barriers and have passed the limitations of conventional sciences. This is the reason why nanoparticles have been evaluated for the use in many fields. InTech publisher and the contributing authors of this book in nanoparticles are all overconfident to invite all scientists to read this new book. The book's potential was held until it was approached by the art of exploring the most advanced research in the field of nano-scale particles, preparation techniques and the way of reaching their destination. 25 reputable chapters were framed in this book and there were alienated into four altered sections; Toxic Nanoparticles, Drug Nanoparticles, Biological Activities and Nano-Technology.
Author: S.V. Bhat
Publisher: Springer Science & Business Media
ISBN: 9401003289
Category : Science
Languages : en
Pages : 273
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Book Description
As biomaterials are used in medical devices, meeting needs in such diverse surgical disciplines as ophthalmology, cardiology, neuromuscular surgery, orthopaedics, dentistry, etc., they must have intimate contact with patient's tissue or body fluids, providing a real physical interface which seriously restricts developments. This book is written for those who would like to advance their knowledge of biomaterials. The subject matter of the book is divided into twelve chapters dealing with the structure and relationship of biological and man-made biomaterials. The application of these materials for various medical devices, and recent developments in tissue engineering, are also discussed.
Author: Clive R. Wood
Publisher: World Scientific
ISBN: 1848166281
Category : Medical
Languages : en
Pages : 490
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Book Description
Antibody-based therapeutics are a central driver of the success of biopharmaceuticals. The discovery technology of this field is isolated to a limited number of centers of excellence in industry and academia. The objective of this volume is to provide a series of guides to those evaluating and preparing to enter particular areas within the field. Each chapter is written with a historical perspective that sets into context the significance of the key developments, and with the provision of “points to consider” for the reader as a value-added feature of the volume. All contributors are experts in their fields and have played pivotal roles in the creation of the technology.
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: William R Wagner
Publisher: Academic Press
ISBN: 0128161388
Category : Technology & Engineering
Languages : en
Pages : 1612
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Book Description
The revised edition of the renowned and bestselling title is the most comprehensive single text on all aspects of biomaterials science from principles to applications. Biomaterials Science, fourth edition, provides a balanced, insightful approach to both the learning of the science and technology of biomaterials and acts as the key reference for practitioners who are involved in the applications of materials in medicine.This new edition incorporates key updates to reflect the latest relevant research in the field, particularly in the applications section, which includes the latest in topics such as nanotechnology, robotic implantation, and biomaterials utilized in cancer research detection and therapy. Other additions include regenerative engineering, 3D printing, personalized medicine and organs on a chip. Translation from the lab to commercial products is emphasized with new content dedicated to medical device development, global issues related to translation, and issues of quality assurance and reimbursement. In response to customer feedback, the new edition also features consolidation of redundant material to ensure clarity and focus. Biomaterials Science, 4th edition is an important update to the best-selling text, vital to the biomaterials’ community. The most comprehensive coverage of principles and applications of all classes of biomaterials Edited and contributed by the best-known figures in the biomaterials field today; fully endorsed and supported by the Society for Biomaterials Fully revised and updated to address issues of translation, nanotechnology, additive manufacturing, organs on chip, precision medicine and much more. Online chapter exercises available for most chapters
Author: Challa S. S. R. Kumar
Publisher: Wiley-VCH
ISBN:
Category : Medical
Languages : en
Pages : 448
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Book Description
This first comprehensive overview on nanotechnological approaches to cancer therapy brings together therapeutic oncology and nanotechnology, showing the various strategic approaches to selectively eliminating cancerous cells without damaging the surrounding healthy tissue. The strategies covered include magnetic, optical, microwave and neutron absorption techniques, nanocapsules for active agents, nanoparticles as active agents, and active and passive targeting, while also dealing with fundamental aspects of how nanoparticles cross biological barriers. A valuable single source gathering the many articles published in specialized journals often difficult to locate for members of the other disciplines involved.
Author: James E. Barrett
Publisher: Springer Nature
ISBN: 3030353621
Category : Medical
Languages : en
Pages : 466
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Book Description
Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
