Receptor Mediated Endocytosis

In this book, skilled experts provide the most up-to-date, step-by-step laboratory protocols for examining molecular machinery and biological functions of exocytosis and endocytosis in vitro and in vivo. The book is insightful to both newcomers and seasoned professionals. It offers a unique and highly practical guide to versatile laboratory tools developed to study various aspects of intracellular vesicle trafficking in simple model systems and living organisms.

Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. • Helps readers understand progress in drug delivery research and applications • Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics • Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics • Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics delivery

This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.

This volume focuses exclusively on those endocytic processes that sequester proteins by a selective, receptor-mediated mechanism. In such an endocytic process, cell surface receptors specifically bind protein ligands and localize them to specialized invaginations of the plasma membrane. These regions are coated pits, so named because they are lined on the cytoplasmic face with an ordered array of the protein, clathrin. It is this 'coat' which provides their characteristic electron microscopic image. Subsequently, these regions pinch off to form coated vesicles which rapidly lose their 'coat' and then fuse with other organelles or the plasma membrane. The hallmarks of ,this process are the specific receptors, coated pits, coated vesicles and an ordered sequence of transit events leading to delivery to selected locations. Receptor recognition, specific disposition of the endocytosed ligand and the existence of recep tor-ligand complexes at highest density in coated pits define the process as selective and concentrative. This topic has received ever increasing attention during the past few years. The evolving mechanisms are especially exciting because they come at a time when the conventional views based on thermodynamic arguments suggest that proteins should not be able to cross into the cell. Receptor-mediated endocytosis, however, reconciles the view that biological membranes should be impervious to macromolecules with the evidence that certain mac romolecules do gain entrance into the cell. During the last few years this field has been stimulated by studies on the uptake and processing of low density lipoproteins (LDL) by cells.

Mononuclear phagocytes, which include macrophages, monocytes and their precursor cells, are the most important cells in the host defence against micro-organisms and tumor cells. During the last twenty-five years research on the biology of mononuclear phagocytes has increased tremendously. This motivated Professor R. van Furth to organize five international conferences on this subject in Leiden, the Netherlands. The edited proceedings of these meethings were published: in 1970 Mononuclear Phagocytes; in 1975 Mononuclear Phagocytes in Immunity, Infections and Pathology; in 1980 Mononuclear Phagocytes -- Functional Aspects; and in 1985 Mononuclear Phagocytes -- Characteristics, Physiology and Function. Reviews of these volumes, published in international journals, praised them as the most up-to-date state of the art publications. The publication of 1991 includes 88 chapters written by more than 200 authors.

"Yet another cell and molecular biology book? At the very least, you would think that if I was going to write a textbook, I should write one in an area that really needs one instead of a subject that already has multiple excellent and definitive books. So, why write this book, then? First, it's a course that I have enjoyed teaching for many years, so I am very familiar with what a student really needs to take away from this class within the time constraints of a semester. Second, because it is a course that many students take, there is a greater opportunity to make an impact on more students' pocketbooks than if I were to start off writing a book for a highly specialized upper- level course. And finally, it was fun to research and write, and can be revised easily for inclusion as part of our next textbook, High School Biology."--Open Textbook Library.

This comprehensive encyclopedic reference provides rapid and focused information about topics of cancer research for the clinical and basic scientist, students and informed laymen. It will be readily accessible, both electronically and in print, such that it will be of value to both the scientific community and the public.