Organelle and Molecular Targeting

Dr. Lara Scheherazade Milane is the Bouvé College of Health Sciences Distinguished Educator (2021) and Assistant Teaching Professor in the Department of Pharmaceutical Sciences, Northeastern University, Boston, MA. Her research interests include mitochondrial nanomedicine and developing nanotechnology based solutions to manipulate cell communication. Dr. Milane is particularly interested in applications for treating multidrug resistant cancer and neurodegenerative diseases. Dr. Milane is also an advocate for women in science, and has 21 peer-reviewed articles, 3 white papers, and 5 book chapters. Dr. Mansoor M. Amiji is the University Distinguished Professor, Professor of Pharmaceutical Sciences, and Professor of Chemical Engineering at Northeastern University in Boston, MA. His primary areas of research interest are in the development of targeted therapeutic solutions for chronic diseases such as cancer, neurodegenerative diseases, and inflammatory diseases. Dr. Amiji has edited 10 books including Applied Physical Pharmacy (now in 3rd edition), Nanotechnology for Cancer Therapy (Taylor & Francis, 2007), Handbook of Materials for Nanomedicine (Pan Stanford Publishing, 2010), and Diagnostic and Therapeutic Applications of Exosomes in Cancer (Elsevier, 2018) along with over 70 published book chapters, and over 360 peer-reviewed articles.

With the advent of the molecular therapeutics era surpassing the omics era, the specialization in molecular therapies and nanotechnology solutions have made rapid strides in organelle targeting. The fast-paced development of SARS-CoV-2 vaccines, such as the mRNA vaccines encoding the viral spike protein, demonstrates the need and capability of molecular therapies and sophisticated nanotechnology-based solutions for drug delivery. While effectively targeting organelles such as mitochondria have therapeutic applications for diseases such as myopathies, cancer, neurodegeneration, progerias, diabetes, and the natural aging process, the exploitation of endoplasmic reticulum as demonstrated in the evelopment of the SARS-CoV-2 vaccine only further emphasizes the importance of organelle targeting and molecular therapeutics. This is an excellent book on organelle and molecular targeting, which will appeal to students, scientists, and clinicians. The purpose of the book, according to the authors, is to summarize the current advancements and principles of molecular and organelle targeting with the hope that this will advance the future of the molecular therapeutics era. I absolutely agree with the authors given the success of the development of the SARS-CoV-2 vaccines. These are indeed very worthy objectives. The book does meet these objectives by, in the first section of the book, summarizing organism-level and tissue-level barriers and cellular localizations and, in the second section, discussing the important concepts of overcoming cellular barriers for specific organelle and molecular targeting. The book is written for students, scientists, and clinicians. In my opinion, the book will also appeal to pulmonologists, cardiologists, gastroenterologists, oncologists, neurologists, and immunologists. The book does meet the needs of the intended audience. The authors are credible authorities in this field based on their credentials and publication records. The book is divided into two sections. The first section is sub-divided into 10 chapters and the second section is sub-divided into eight chapters. The first section of the book starts with an introduction on organism-level and tissue-level barriers and cellular localization. The first chapter deals with the route of administration, distribution, and tissue-specific challenges.Other chapters discuss essentials of nanomedicine and drug-delivery approaches, escaping immune clearance, tumor targeting, and targeting immune cells and dysfunction. The chapter on escaping immune clearance discusses stealth functionalization, a chemical approach to prolong the blood circulation of nanoparticles (NPs) in the human host to ensure targeted delivery by means of achieving stealth functionality through polymer grafting. The construction ofplatelet-derived nanoparticles (PNPs) by wrapping platelet membranes onto solid NP cores and how they target passively using natural markers on the cell surface or actively through engagement with specific markers such as CLEC-2, P-selectin, and specific integrins is quite interesting. The chapter on tumor targeting discusses how systemic side effects of cytotoxic chemotherapy could be minimized by the development of tumor targeted therapy specific for receptor mutations or proteins that regulate cellular functions and gene expression in tumor cells. The description of various signal transduction inhibitors is very interesting. The second section of the book discusses the various approaches of overcoming cellular barriers such as the plasma membrane and mucus barriers. Another interesting chapter deals with how the lysosomes serve as a signaling hub and how targeting therapies for lysosomes have therapeutic indications in cancer, neurodegenerative diseases, autoimmune diseases, and other indications such as lysosomal storage diseases, infectious diseases, and cardiovascular diseases. Other chapters discuss how microtubule targeting is helpful in cancer treatment. There is an interesting chapter on the importance of localizing therapeutics to the endoplasmic reticulum with several illustrations. An independent chapter on targeting mitochondria explains how mitochondrial nanomedicine could be helpful in the treatment of cancer. The chapter on directed therapies to nucleic acid and cytoplasmic RNA provides extensive coverage on RNA and the importance of targeting cytoplasmic RNA and current methods to target DNA and RNA. There is an interesting discussion on mRNA vaccines for COVID-19. The concluding chapter of the book deals with practical considerations for engineering nanoparticles for subcellular organelle targeting. Strategies to target the nucleus, mitochondria, and other subcellular targets like dendritic cells and exosomes are discussed. Characterization and evaluation of subcellular localization of nanomaterials using flourescence-tagged systems such as Flourescence Lifetime Imaging Microscopy (FLIM) and Rotor-Based Organelle Viscosity Imaging is discussed (ROVI). The book includes several high-quality colored illustrations making the subject matter easily understandable. The index is quite helpful in easy localization of the various topics of interest.This is an excellent book on organelle and molecular targeting, which will be quite useful for its intended audience including students, scientists, and clinicians, especially oncologists, gastroenterologists, cardiologists, neurologists, pulmonologists, and immunologists. Omer Iqbal, MD, FACC, FESC(Loyola University Medical Center)

• Preface. Acknowledgments. Editors. Contributors. SECTION ONE: INTRODUCTION: ORGAN, TISSUE, AND CELLULAR LOCALIZATION. Route of Administration, Distribution, and Tissue-Specific Challenges. Nanomedicine and Drug Delivery Approaches. Escaping Immune Clearance. Passive Drug Delivery, Mechanisms of Uptake, and Intracellular Trafficking. Tumor Targeting. Localizing Therapeutics to the Brain. Pulmonary Drug Delivery. Cardiovascular Drug Delivery. Localizing Therapeutics to the Gastrointestinal System. Targeting Immune Cells and Dysfunction. SECTION TWO: OVERCOMING CELLULAR BARRIERS. Overcoming the Plasma Membrane. Overcoming the Mucus Barrier. Directing Therapies to Lysosomes. Microtubule Targeting in Cancer Treatment. Localizing Therapeutics to the Endoplasmic Reticulum. Targeting Mitochondria. Directed Therapies to Nucleic Acid and Cytoplasmic RNA. Considerations for Engineering Nanoparticles for Achieving Subcellular Organelle Targeting. Index.