Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies
DOWNLOAD
Download Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies PDF/ePub or read online books in Mobi eBooks. Click Download or Read Online button to get Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies book now. This website allows unlimited access to, at the time of writing, more than 1.5 million titles, including hundreds of thousands of titles in various foreign languages. If the content not found or just blank you must refresh this page
Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies
DOWNLOAD
Author :
language : en
Publisher:
Release Date : 2014
Optimization Of Near Infrared Bifunctional Cancer Imaging And Photodynamic Therapy Agents Through Structure Activity Relationship Studies written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
Cancer imaging has an important role in the detection and diagnosis both before and after anti-cancer treatment. In certain clinical interventions such as surgery, there remains an unmet need to have real time imaging techniques which can assist the surgeon in complete resection of tumors. In highly inflamed areas such as tumor margins, it can be exceptionally difficult to distinguish between normal and malignant tissue. Fluorescence optical imaging is a real time imaging modality which could aid in distinguishing tumor and non-tumor tissue through the use of tumor specific fluorescence agents (fluorophores). The practice of using these fluorophores to assist in discerning malignant tissue is a clinical practice known as image guided therapy. This technique is still being validated and can be improved upon with the use of better fluorophores which would allow clinicians to detect malignant cells deeper in tissue. Deeper detection can occur through the use of near-infrared (NIR) fluorophores which absorb light at wavelengths where there is little interference and hindrance from endogenous light absorbers present in patient. Additionally, another light based intraoperative practice such as photodynamic therapy (PDT) might be further able to enhance long term survival outcomes. PDT could work in this setting to further destroy cancerous tissue but in a less invasive manner than surgery. Previous work from our laboratory has revolved around the deep red absorbing chlorophyll-a derivate 3-(1'-hexyloxy)ethyl-3-devinyl-pyropheophorbide-a (HPPH). In our laboratory's work, we have shown that HPPH is an exceedingly well tolerated second generation photosensitizer which can effectively improve survival outcome with PDT.^Our laboratory used these abilities of HPPH and in the first of its kind study, HPPH was conjugated to a NIR absorbing cyanine dye (CD) to develop a single agent which could use long wavelength light for selective fluorescence detection and PDT treatment of tumors. While imaging and treatment was successful with this compound, it also had a few drawbacks. One of the problems encountered was the high amount of bifunctional drug required to successfully treat the tumor by PDT verses the HPPH alone. It is believed that this was due to quenching of singlet oxygen by the CD upon activation of the PS and also due to energy transfer through F©œrster Resonance Energy Transfer (FRET). Therefore, we hypothesize that structure activity relationship studies (SAR) on a series of imaging and therapeutic agents will enable us to develop a single agent with near infrared fluorescence image guided photodynamic therapy.^One strategy to develop an image guided agent through a new porphyrin-cyanine dye conjugate is to develop a more tumor selective cyanine dye. In Aim I of this work we used structure activity relationship (SAR) to design and synthesize a series of IR820 cyanine dye derivatives with various functional groups around their periphery. Favorable in vivo tumor selectivity over normal tissue, retention time in tumor, and photophysical properties all factored into determining which of those substituents would be further pursued. These studies showed that introduction of 4-aminophenylthiol to IR820 resulted in the most favorable cyanine dyes being created. Substitution of the amine functionality or removal of the sulfur group gave suboptimal results thereby validating the importance of the entire 4-aminophenylthioether group.^While not as substantial in yielding a favorable cyanine dye, studies from Aim I also showed N-alkyl sufonate was preferential over N-alkylcarboxylic acid and that modification occurring meso to the 4-aminophenylthiol did not greatly alter the favorable drug profile. To further improve our lab's approach to a making image guided agents, Aim II sought to overcome the deficiencies of the photosensitizer-cyanine dye conjugate by complexing the heavy metals indium, gallium, and palladium within the porphyrin core. This approach was taken because previous studies have shown that metallation can reduce FRET and also increase singlet oxygen yields. Our studies showed that indium and palladium compounds generated more singlet oxygen than the non-metallated HPPH-CD and also reduced FRET. However, it was the introduction of indium within the HPPH of the conjugate that had the most favorable effects. Studies with the In(III)HPPH-CD compound showed favorable in vivo tumor selectivity and high in vitro/vivo PDT efficacy. In attempts to further improve upon In(III)HPPH-CD, the effect of varying the linker length between the porphyrin and CD were analyzed. Extending the linker length was thought to increase the spatial separation between the HPPH from CD moieties. This effect was seen with the longest linker length compound of 6 carbons as reduction in FRET and photobleaching were shown in vitro. However, in vivo PDT efficacy studies ultimately showed limited benefits in extending the linker length versus the original In(III)HPPH-CD. As the lead compound, in depth studies were performed with In(III)HPPH-CD to examine its toxicity profile. While well tolerated at the therapeutic dose, histopathological renal lesions were noted during post-mortem necropsy examinations in animals dosed with high amounts of drug. This renal toxicity is believed to be caused by free indium and therefore we are assessing ways to resolve this issue through administration of purer compound and delivery of more tumor selective agents. The final approach of this study for the development of NIR image guided agents was to use the NIR absorbing bacteriochlorin class of photosensitizers. Through preliminary SAR studies previously performed in our laboratory, two lead candidates were established. In Aim III of this work, full biological analysis was performed on the methyl ester and carboxylic acid derivatives of 3-(1-butoxy)ethyl-3-deacetylbacteriopurpurin-18-N-butylimide. Early in vitro studies examining uptake and PDT efficacy suggested the carboxylic acid derivative to be an improved agent over the methyl ester analog.^However, when tested in vivo, the methyl ester compound was observed to have significantly higher tumor selectivity which in turn resulted in >60% long term PDT survival outcome in tumor bearing mice vs. 14% with the carboxylic acid derivative. In addition to in vivo PDT efficacy, the methyl ester bacteriochlorin was also found to have minimal phototoxicity in normal tissue, favorable biodistribution as measured by 14C radiotracing, and minimal drug toxicity. Another observation from this study was that the lead bacteriochlorin exists as an epimeric mixture of two stereoisomers and their purification by HPLC was also performed. While in vivo work is still in preliminary phases, in vitro studies suggest minimal differences exist between the two isomers and the epimeric mixture. Overall, we have demonstrated the benefit that rational drug design through SAR can have on the development of bifunctional agents which can be used for both fluorescence optical imaging and photodynamic therapy. The compounds established from this work have been designed to have favorable optical imaging capabilities, tumor selectivity, and therapeutic potential. It is these characteristics that make the agents ideal candidates for further studies into their ability to be used as real time image guided therapeutic agents for the improvement of long term survival rates.
Ruthenium Complexes
DOWNLOAD
Author : Alvin A. Holder
language : en
Publisher: John Wiley & Sons
Release Date : 2018-02-27
Ruthenium Complexes written by Alvin A. Holder and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-02-27 with Science categories.
Edited by a team of highly respected researchers combining their expertise in chemistry, physics, and medicine, this book focuses on the use of rutheniumcontaining complexes in artificial photosynthesis and medicine. Following a brief introduction to the basic coordination chemistry of ruthenium complexes and their synthesis in section one, as well as their photophysical and photochemical properties, the authors discuss in detail the major concepts of artificial photosynthesis and mechanisms of hydrogen production and water oxidation with ruthenium in section two. The third section of the text covers biological properties and important medical applications of ruthenium complexes as therapeutic agents or in diagnostic imaging. Aimed at stimulating research in this active field, this is an invaluable information source for researchers in academia, health research institutes and governmental departments working in the field of organometallic chemistry, green and sustainable chemistry as well as medicine/drug discovery, while equally serving as a useful reference also for scientists in industry.
Antibody Fusion Proteins
DOWNLOAD
Author : Steven M. Chamow
language : en
Publisher: Wiley-Liss
Release Date : 1999-04-13
Antibody Fusion Proteins written by Steven M. Chamow and has been published by Wiley-Liss this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-04-13 with Science categories.
Thoroughly detailed and illustrated, this book examines the construction, properties, applications, and problems associated with specific types of fusion molecules used in clinical and research medicine. The editors present an overview of the field, followed by nine chapters divided into two general sections based on the two primary parts of the antibody molecule: Fab fusion proteins and Fc fusion proteins. In addition, numerous renowned scientists in the field have contributed outlines demonstrating man-made molecules that will be required not only to overcome the limitations of monoclonal antibodies, but also to extend the principle of selective targeting. Divided into specific, accessible sections, Antibody Fusion Proteins includes: * Chapters describing Fc fusion proteins, as well as several classes of antigen-binding proteins * Complete details on the design and molecular construction of genetically engineered fusion molecules * Useful information on molecular purification, large-scale production, practical applications, and their therapeutic potential * The latest data on forming fusion proteins with toxins, cytokines, or enzymes that can activate a prodrug
Drug Selectivity
DOWNLOAD
Author : Norbert Handler
language : en
Publisher: John Wiley & Sons
Release Date : 2018-02-27
Drug Selectivity written by Norbert Handler and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-02-27 with Medical categories.
The book "Drug Selectivity - An Evolving Concept in Medicinal Chemistry" provides a current overview and comprehensive compilation for medicinal chemists that discusses the effects of aiming for multiple targets on the entire drug development process. The result is a broad survey of current and future strategies for drug selectivity in medicinal chemistry with theoretical but also practical aspects. Different strategies are presented and evaluated, such as various design approaches, merged multiple ligands, discovery technologies and a broad range of successful examples of unselective drugs taken from all major disease areas. With its wide-ranging view of an emerging new paradigm in drug development, this handbook is of prime importance for every medicinal and pharmaceutical chemist.
Radioguided Surgery
DOWNLOAD
Author : Giuliano Mariani
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-05-10
Radioguided Surgery written by Giuliano Mariani and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-05-10 with Medical categories.
This multidisciplinary textbook is designed to be the standard on the subject and is geared for use by physicians who are involved in the care and/or diagnosis of cancer patients. Comprehensive coverage is provided on all aspects of radioguided surgery. Practical information is readily accessible and throughout there is an emphasis on improved decision making. Tables present the indications, performance, and interpretation of procedures at a glance. A wealth of illustrations, including a full-color insert, enhances the application of new concepts.
In Vivo Fluorescence Imaging
DOWNLOAD
Author : Mingfeng Bai
language : en
Publisher: Humana
Release Date : 2016-06-10
In Vivo Fluorescence Imaging written by Mingfeng Bai and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-06-10 with Medical categories.
This detailed volume includes a rich variety of applications using various instrumentations, probes, disease models, and targets in order to account for the multidisciplinary nature of the use of in vivo fluorescence imagine. The book also includes chapters on the emerging fields of cell tracking, image-guided treatment, and fluorescence imaging in the second NIR window, as well as protocols for evaluation methods before and after in vivo imaging. Written for the highly successful Methods in Molecular Biology series, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, In Vivo Fluorescence Imaging: Methods and Protocols serves as a valuable reference for researchers from numerous fields who wish to become more familiar with in vivo fluorescence imaging techniques.
Carbon Nanomaterials For Biomedical Applications
DOWNLOAD
Author : Mei Zhang
language : en
Publisher: Springer
Release Date : 2015-11-06
Carbon Nanomaterials For Biomedical Applications written by Mei Zhang and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-11-06 with Technology & Engineering categories.
This book covers a wide range of topics relating to carbon nanomaterials, from synthesis and functionalization to applications in advanced biomedical devices and systems. As they possess unique and attractive chemical, physical, optical, and even magnetic properties for various applications, considerable effort has been made to employ carbon nanomaterials (e.g., fullerenes, carbon nanotubes, graphene, nanodiamond) as new materials for the development of novel biomedical tools, such as diagnostic sensors, imaging agents, and drug/gene delivery systems for both diagnostics and clinical treatment. Tremendous progress has been made and the scattered literature continues to grow rapidly. With chapters by world-renowned experts providing an overview of the state of the science as well as an understanding of the challenges that lie ahead, Carbon Nanomaterials for Biomedical Applications is essential reading not only for experienced scientists and engineers in biomedical and nanomaterials areas, but also for graduate students and advanced undergraduates in materials science and engineering, chemistry, and biology.
Chemical Aspects Of Photodynamic Therapy
DOWNLOAD
Author : Raymond Bonnett
language : en
Publisher: CRC Press
Release Date : 2000-08-07
Chemical Aspects Of Photodynamic Therapy written by Raymond Bonnett and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-08-07 with Science categories.
Photodynamic therapy (PDT) is a ground breaking medical technique which uses lasers to activate light-sensitive chemicals to treat cancer and other diseases without resorting to surgery. For the first time, Chemical Aspects of Photodynamic Therapy introduces in an accessible way the physics, chemistry and biology behind the technique. This highly a
Near Infrared Emitting Nanoparticles For Biomedical Applications
DOWNLOAD
Author : Antonio Benayas
language : en
Publisher: Springer Nature
Release Date : 2020-04-13
Near Infrared Emitting Nanoparticles For Biomedical Applications written by Antonio Benayas and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-04-13 with Technology & Engineering categories.
This book analyzes and evaluates the growing field of light-emitting nanoprobes as contrast agents for in vivo imaging and sensing. It is a comprehensive resource that critically analyzes the state of the art in an interdisciplinary manner, with a special focus on the shift of emission wavelengths into the near-infrared (NIR) spectral region (ranging from 0.7 to 2 microns), which has greatly contributed to the latest advances in biomedical imaging and sensing. This book discusses merits of different contrast agents at nanoscale, and how their unique chemical and structural properties lead to the emission and interaction of light within the NIR window. Both the NIR-emitting materials and various surface modification strategies governing their interactions with the biological system at the “nano” level are discussed. Furthermore, different experimental techniques and protocols for NIR-light-based in vivo imaging and sensing are addressed to shed light on further understanding of the advantages and limitations of each category of these nanoprobes. Assembles the state of the art heretofore appearing in scientific literature into a comprehensive, multi-perspective guidebook on near infrared-emitting nanomaterials in an assortment of biomedical applications; Explains the physical, chemical, and biological phenomena underlying near infrared-emitting nanomaterials for biomedical applications; Presents conceptual and experimental approaches surrounding a unique spectral range of light emission from nanosized contrast agents, while offering a clear explanation of basic and general phenomena regarding the interaction between light and biological tissues, such as absorption, scattering and autofluorescence.
Handbook Of Photodynamic Therapy Updates On Recent Applications Of Porphyrin Based Compounds
DOWNLOAD
Author : Ravindra K Pandey
language : en
Publisher: World Scientific
Release Date : 2016-03-24
Handbook Of Photodynamic Therapy Updates On Recent Applications Of Porphyrin Based Compounds written by Ravindra K Pandey and has been published by World Scientific this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-03-24 with Science categories.
The main objective of this book is to present the recent applications of photodynamic therapy (PDT) in treating cancer and other diseases. The limitations associated with current PDT agents, and the synthetic designs that have been used in various laboratories are also discussed. The utility of certain tumor-avid agent for cancer imaging (fluorescence, PET, MRI) is also summarized. The book also includes the use of delivery vehicles, including nanoparticles in improving the tumor-specificity of the desired agents. The book is basically focused on the translational approach of drug development. By providing certain specific examples, a clear concept of moving a 'product' from the bench to bed-side is also discussed.To have a clear concept of drug development the book is divided in three parts — Medicinal Chemistry, Mechanistic and Clinical studies. Each part includes the contributions from the leading scientists with extensive experience in the respective field. The handbook is assembled by renowned scientists Dr Dougherty, known as the father of PDT, Dr Kessel, well known for his contributions on mechanism of PDT and Dr Pandey for his inventions in developing improved agents for PDT and cancer-imaging.