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Organelle and Molecular Targeting




ISBN 9780367551377
Published December 28, 2021 by CRC Press
510 Pages 84 Color & 15 B/W Illustrations

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Book Description

We have surpassed the omics era and are truly in the Age of Molecular Therapeutics. The fast-paced development of SARS-CoV-2 vaccines, such as the mRNA vaccines encoding the viral spike protein, demonstrated the need for and capability of molecular therapy and nanotechnology-based solutions for drug delivery. In record speed, the SARS-CoV-2 viral RNA genome was sequenced and shared with the scientific community, allowing the rapid design of molecular therapeutics. The mRNA vaccines exploit the host cell endoplasmic reticulum to produce viral spike proteins for antigen presentation and recognition by the innate and adaptive immune system. Lipid nanoparticles enable the delivery of the fragile, degradation-sensitive nucleic acid payloads. Molecular-based therapeutics and nanotechnology solutions continue to drive the scientific and medical response to the COVID-19 pandemic as new mRNA, DNA, and protein-based vaccines are developed and approved and the emergency use approved vaccines are rapidly manufactured and distributed throughout the globe.

The need for molecular therapies and drug delivery solutions is clear, and as these therapies progress and become more specialized there will be important advancements in organelle targeting. For example, using organelle targeting to direct lipid nanoparticles with mRNA payloads to the endoplasmic reticulum would increase the efficacy of mRNA vaccines, reducing the required dose and therefore the biomanufacturing demand. Likewise, improving the delivery of DNA therapeutics to the nucleus would improve efficacy. Organelles and molecules have always been drug targets, but until recently we have not had the tools or capability to design and develop such highly specific therapeutics. Organelle targeting has far-reaching implications. For example, mitochondria are central to both energy production and intrinsic apoptosis. Effectively targeting and manipulating mitochondria has therapeutic applications for diseases such as myopathies, cancer, neurodegeneration, progerias, diabetes, and the natural aging process. The SARS-CoV-2 vaccines that exploit the endoplasmic reticulum (for mRNA vaccines) and the nucleic translational process (DNA vaccines) attest to the need for organelle and molecular therapeutics. This book covers the status, demand, and future of organelle- and molecularly targeted therapeutics that are critical to the advancement of modern medicine. Organelle and molecular targeting is the drug design and drug delivery approach of today and the future; understanding this approach is essential for students, scientists, and clinicians contributing to modern medicine.

Table of Contents

Preface

Acknowledgments

Editors

Contributors

SECTION ONE: INTRODUCTION: ORGAN, TISSUE, AND CELLULAR LOCALIZATION

1. Route of Administration, Distribution, and Tissue-Specific Challenges

Melis Debreli Coskun and Jonghan Kim

2. Nanomedicine and Drug Delivery Approaches

Carla Vitorino, Carla M. Lopes, and Marlene Lucio

3. Escaping Immune Clearance

Esmael M. Alyami, Ammar Tarar, and Ching-An Peng

4. Passive Drug Delivery, Mechanisms of Uptake, and Intracellular Trafficking

Parisa Foroozandeh, Siti Asmaa Mat Jusoh, and Shaharum Shamsuddin

5. Tumor Targeting

Eva Y. Pan, Aubrey Johnson, and Jennifer Zhao

6. Localizing Therapeutics to the Brain

Sakshi Hans, Karrina McNamara, Eoghan Cunnane, Aisling M. Ross, Lara Milane, John J.E. Mulvihill, and Andreas M. Grabrucker

7. Pulmonary Drug Delivery

Basanth Babu Eedara, Wafaa Alabsi, David Encinas-Basurto, Robin Polt,

Don Hayes Jr, Stephen M. Black, and Heidi M. Mansour

8. Cardiovascular Drug Delivery

Jingyan Han, Jena B. Goodman, Mo Zhang, and Zhaoyuan Li

9. Localizing Therapeutics to the Gastrointestinal System

Chunhua Yang and Didier Merlin

10. Targeting Immune Cells and Dysfunction

Lara Scheherazade Milane

SECTION TWO: OVERCOMING CELLULAR BARRIERS

11. Overcoming the Plasma Membrane

Nuno Bernardes and Arsenio M. Fialho

12. Overcoming the Mucus Barrier

Janni Støvring Mortensen, Mai Bay Stie, Stine Harloff-Helleberg, and Hanne Mørck Nielsen

13. Directing Therapies to Lysosomes

Satya Siva Kishan Yalamarty, Xiang Li, Nina Filipczak and Vladimir Torchilin

14. Microtubule Targeting in Cancer Treatment

Abdulaziz Alhussan, Sarah Eaton, Nicholas Palmerley and Devika B. Chithrani

15. Localizing Therapeutics to the Endoplasmic Reticulum

Lara Scheherazade Milane

16. Targeting Mitochondria

Lara Scheherazade Milane

17. Directed Therapies to Nucleic Acid and Cytoplasmic RNA

Mitali Ghose

18. Considerations for Engineering Nanoparticles for Achieving Subcellular Organelle Targeting

Ketki Bhise, Katyayani Tatiparti, Somrita Dey, Kushal Vanamala, Ayatakshi Barari, Samaresh Sau, and Arun K. Iyer

Index

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Editor(s)

Biography

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.

Reviews

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)