Nucleic Acids as Gene Anticancer Drug Delivery Therapy

Loutfy H. Madkour

• Publisher: Academic Press
• Year: 2019
• ISBN:
  9780128197783
• Topic: Biowissenschaften
• Subtopic: Genetik & Genomik

Nucleic Acids as Gene Anticancer Drug Delivery Therapy highlights the most recentdevelopments in cancer treatment using nucleic acids, nanoparticles and polymer nanoparticles for genomic nanocarriers as drug delivery, including promising opportunities for targeted and combination therapy. The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention.This book presents the use of nanotechnology for medical applications, focusing on its use for anticancer drug delivery. Various intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery are discussed.The use of smart drug delivery systems seems to be a promising approach for developing intelligent therapeutic systems for cancer immunotherapies and is discussed in detail along with nucleic acid-targeted drug delivery combination therapy for cancer. Nucleic Acids as Gene Anticancer Drug Delivery Therapy will be a useful reference for pharmaceutical scientists, pharmacologiests, and those involved in nanotechnology and cancer research.

• Discusses intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery
• Contains a comprehensive comparison of various delivery systems, listing their advantages and limitations
• Presents combination therapy as a new hope for enhancing current gene-based treatment efficacy

Chapter 1

Advanced drug delivery systems: New nanomedication technologies

Abstract

We begin by studying the importance of nanotechnology for health design, a subject commonly known as nanomedicine. Nanomedicine offers unique advantages in treating human cancers. We discuss nanotechnology-based drug delivery in cancer. The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention. The use of lipid-based vesicles is a very promising approach to treating diseases such as cancer, chronic infections, and autoimmunity. We employ effective nucleic acid combinations to obtain more comprehensive outcomes, highlighting the critical factors involved in successful therapy. We present a classification of biodegradable polymers used in drug delivery systems. We briefly discuss some applications and advantages of nanoparticle drug carriers. We conclude with the author’s perspective on the future of combinational therapy using nucleic acid therapeutics, articulating the main challenges to advancing this promising approach to the clinical realm.

Keywords

Nanotechnology; Nanomedical technology; Polymeric nanoparticles; Drug delivery; Drug carriers; Cancer

Nanotechnology is increasingly considered the technology of the future. Nanotechnology allows scientists to acquire the necessary abilities to understand and manipulate materials at the scale of atoms and molecules—materials that have the following key properties:

• ● dimensions in the range 1–100 nm
• ● designed using methodologies that exhibit fundamental control over the physical and chemical attributes of molecular-scale structures.

Nanotechnology research has brought about advances in communications, engineering, chemistry, physics, robotics, biology, and medicine. Nanotechnology has been utilized in medicine for therapeutic drug delivery and the development of treatments for a variety of diseases and disorders—hence the very significant advances in these disciplines.

Nanotechnology could be defined as the technology that enabled the control, manipulation, study, and manufacture of structures and devices in the nanometer-size range. Nano-sized objects (e.g., nanoparticles) take on novel properties and functions that differ markedly from those seen in items made of identical materials.

1.1 Nanotechnology of health design

Nanotechnology has firmly entered the realm of drug delivery. The performance of intelligent drug delivery systems is continuously improving with the purpose of maximizing therapeutic activity and minimizing undesirable side effects. The small size, customized surface, improved solubility, and multifunctionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases like cancer.

The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention. These technological innovations, called nanomedicine by the National Institutes of Health, have the potential to make molecular discoveries arising from genomics and proteomics of widespread benefit for patients. Nanoparticles can mimic or alter biological processes (e.g., infection, tissue engineering, and de novo synthesis). These devices include, but are not limited to, functionalized carbon nanotubes, nanomachines (e.g., constructed from interchangeable DNA parts and DNA scaffolds), nanofibers, self-assembling polymeric nanoconstructs, nanomembranes, and nano-sized silicon chips for drug, protein, nucleic acid, or peptide delivery and release, as well as biosensors and laboratory diagnostics.

Advances in nanotechnology have allowed the engineering of sophisticated nanostructures with unique physical characteristics and surface chemistry. These advances show great promise for generating a new class of cancer therapeutics that have distinctive functional capabilities relative to conventional therapeutic agents.

Cancer is an extremely complex disease involving multiple signaling pathways that enable tumor cells to evade programmed cell death, thus making cancer treatment extremely challenging. The use of combination therapy involving both gene therapy and chemotherapy has resulted in enhanced anticancer effects and has become an increasingly important strategy in medicine. Chemotherapy is based on inhibiting the division of rapidly growing cells, a characteristic of cancerous cells, but unfortunately it also affects normal cells with fast proliferation rates, such as hair follicle, bone marrow, and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, and the development of multidrug resistance support the need to find new effective targeted treatments based on changes in the molecular biology of tumor cells. These novel targeted therapies, of increasing interest as evidenced by US Food and Drug Administration (FDA)-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing undesirable side effects. Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities such as surgery or radiation. However, despite the widespread clinical use of combination therapies relatively little attention has been given to the potential of modern nanocarrier delivery methods, such as liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small-molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This book discusses recent advances in the development of delivery methods using combinations of small-molecule drugs and nucleic acid therapeutics to treat cancer.

Nanotechnology has proven beneficial in the treatment of cancer, AIDS, and many other diseases, and in bringing about advances in diagnostic testing. Chemistry plays a key role in the development of innovative synthetic materials to overcome the challenges of producing next-generation gene delivery therapies and protocols. Gene therapy is a technique used to correct defective genes responsible for disease development and may be classified into two types: somatic and germline gene therapy.

The use of proteins and nucleic acids as pharmaceutical agents has been severely limited by an inability to deliver biomolecules into the cytoplasm of target cells. The use of lipid-based vesicles is a very promising approach to treating diseases such as cancer, chronic infections, and autoimmunity. Modern drug encapsulation methods allow the efficient packing of therapeutic substances inside liposomes, thereby reducing the systemic toxicity of drugs. Specific targeting can enhance the therapeutic effect of drugs as they accumulate at the diseased site. In the vaccine field the integration of functional viral envelope proteins into liposomes has led to an antigen carrier and delivery system termed a virosome, a clinically proven vaccine platform for subunit vaccines with an excellent immunogenicity and tolerability profile.

The blood-brain barrier (BBB) in the central nervous system (CNS) is the main limiting factor for specific drug delivery [1]. The delivery of nucleic acids with transient activity for genetic engineering is a promising methodology with potential applications in the treatment of diseases ranging from cancer and infectious diseases to he...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Summary
• About the Author
• Chapter 1: Advanced drug delivery systems: New nanomedication technologies
• Chapter 2: Characteristics of deoxyribonucleic acid
• Chapter 3: Characteristics of ribonucleic acid
• Chapter 4: Clinical applications of nucleic acid (DNA) gene therapeutics delivery systems
• Chapter 5: Therapeutic applications of siRNA gene delivery systems
• Chapter 6: Targeting mechanisms of polymeric micelles for delivery of siRNA in cancer therapy
• Chapter 7: Classifications of DNA binding molecules—Drug interactions
• Chapter 8: Structures of quadruplex nucleic acids and their drug complexes
• Chapter 9: Solvent-accessible surfaces of proteins and nucleic acids
• Chapter 10: Nucleic acid medicines as green novel anticancer drugs
• Chapter 11: Correlation between nucleic acids and nanoparticle therapeutics for cancer treatment
• Chapter 12: Drug delivery systems as advanced nanotechnology
• Chapter 13: Nanoparticle and polymeric nanoparticle-based targeted drug delivery systems
• Chapter 14: Polymer nanoparticle drug-nucleic acid combinations
• Chapter 15: Combinational delivery therapies of nucleic acids for cancer treatment
• Chapter 16: Multiple delivery of drug-nucleic acid combinations for cancer treatment
• Chapter 17: FDA and the medical device clinical drug trials
• Chapter 18: Biological barriers to cancer drug delivery, efficacy and cancer models
• Chapter 19: Toxicological considerations of clinically applicable nanoparticles
• Chapter 20: DNA complexes as an efficient gene anticancer drug delivery therapy
• Chapter 21: Immunotherapy with mRNA vaccination and immunomodulation nanomedicine for cancer therapy
• List of abbreviations
• Index