Nanocarriers for Cancer Diagnosis and Targeted Chemotherapy

Muhammad Raza Shah, Muhammad Imran, Shafi Ullah

• Publisher: Elsevier
• Year: 2019
• Print ISBN: 9780128167731
• eBook ISBN: 9780128163115
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

Nanocarriers for Cancer Diagnosis and Targeted Chemotherapy reviews the principles and applications of nanocarriers for targeted drug delivery. Drug targeting involves active and passive strategies that exploit both the use of ligands for interactions and the physical and chemical properties of nanocarriers and micro-environments at target sites. Multidrug resistance and adverse side effects associated with anticancer drugs have attracted greater scientific attention and led formulation scientists to specifically target these drugs to target sites. Nanocarriers like liposomes, niosomes, gold nanorods, carbon nanotubes, and micelles are discussed for the delivery of drugs to specific disease sites.This is an important reference source for researchers in the biomedical and biomaterials fields who want to gain an understanding on how nanotechnology is used for earlier diagnoses and more effective cancer treatment.- Explores the fundamental principles of drug targeting through different nano-carriers, highlighting major applications- Shows how the use of nanocarriers is leading to quicker cancer diagnosis and more effective treatment- Discusses the major challenges of using nanocarriers for drug delivery and assesses how to overcome these barriers

Chapter 1

Potential physical and biological barriers leading to failure of cancer chemotherapy

Abstract

Cancer is among the deadliest diseases in the world, with millions of new cases reported each year. Chemotherapy is preferred for cancer treatment due to the invasive nature of and other problems associated with surgery, laser therapy, and photodynamic therapy. Currently used chemotherapeutic agents face various issues that limit their effective use for cancer treatment. These issues arise either from the physicochemical properties or biological barriers associated with the tumor microenvironment or biological systems. The physicochemical barriers are associated with the anticancer drugs and include their lower aqueous solubility and membrane permeability, nonselectivity toward cancerous cells, and instability in the intestine due to harsh acidic and enzymatic actions. The biological barriers that reduce the therapeutic efficacy of anticancer drugs include transmembrane drugs’ efflux transporter proteins, presystemic metabolism, nonlinear pharmacokinetics, hepatic impairment and malabsorption, genetic variations, physiological characteristics of tumor tissues and their unique microenvironment, and impediments erected by the blood–brain barrier for successful treatment of brain tumors. This chapter covers both the physicochemical and biological barriers that reduce the therapeutic efficacy of chemotherapeutic agents used for the treatment of various types of cancers.

Keywords

Cancer; chemotherapy; barriers; physicochemical; biological

1.1 Introduction

Cancer is a group of disease where abnormal cell growth and a failure to control it lead to tumor growth that can spread and invade other parts of the body. Cancer starts from an uncontrolled cellular growth to form a heterogeneous primary tumor with premature and leaky vasculature followed by spread or metastasis of the cancer cells to other parts of body to form secondary tumors. The pathogenesis of cancer is very dynamic as it involves constantly altered cellular and molecular interactions in different pathways (Hanahan and Weinberg, 2011).

Cancer has emerged as a major health issue all over the world. An alarming increase in cancer incidence has been predicated by global demographic characteristics for the coming decades, with 420 million new cancer cases annually expected by 2025. Lung, prostate, female breast, and colorectal cancers are the most frequently diagnosed cancers in Europe. Among all the types of cancer, lung cancer is the greatest cause of cancer incidence and mortality around the globe (Ferlay et al., 2013, 2015). People of all societies around the world, women and men, the young and old, the poor and rich, have been badly affected by cancer, which increases the economic burden and mental stress on families, patients, and societies. A substantial number of cancer patients experience a significant reduction in their quality of life due to economic hardship, physical pain, and mental anguish (Xu et al., 2016).

Host–environment interactions and persistent tissue injury are the leading causes of cancer occurrence. Moreover, exposure of carcinogenic agents such as ultraviolet radiations, tobacco, and infections for a longer time results in different epigenetic, genetic, and global transcriptome changes through inflammatory pathways that in turn lead to increased cancer risk and cancer incidence (Hidalgo et al., 2010). The pathogenesis of cancer is very dynamic as it involves constantly altered cellular and molecular interactions in different pathways. Six hallmarks of cancer have been established that can distinguish characteristics between the tumor and normal tissues and may provide better alternative treatments: sustained singling for proliferation, growth suppressors escaping, activation of invasion and metastasis, replicative immortality, induction of angiogenesis, and development of resistance to cell death (Orgogozo et al., 2015). Maintenance of growth signals and continuous proliferation of cancer cells are the prominent characteristics of almost all types of cancers. Similarly, the inhibition of cells’ normal regulators and apoptosis is also associated with cancers. The development of higher resistance in the cells to apoptosis helps the cancer cells to maintain their DNA integrity and thus to keep replicating continuously. Cancer cells get nutrients and dispose their wastes through angiogenesis, the formation of new blood vessels. New or secondary tumors are formed as the cancer cells migrate to new sites. Evasion from immune destruction and establishment of energy metabolism are the two emerging hallmarks of cancer cells. Cancer cells upregulate glucose transporter expression, thus reprogramming their metabolic pathway to “aerobic glycolysis.” The resultant metabolic switch in turn leads to the generation of amino acids and nucleosides, which facilitate additional growth and proliferation. Another important aspect of cancer cells is that T-lymphocytes markers that help in recognition and destruction of abnormal or foreign cells do not get well expressed on cancer cells. This allows the cancerous cells to avoid elimination by the immune system (Jogi et al., 2018; Orgogozo et al., 2015).

Early diagnosis of cancer has been an important point for the treatment of cancer. It has been very difficult to diagnose cancer during early stages as its clinical symptoms show up very often before cancer progresses to an incurable stage. Various treatment strategies are used alone or in combination for achieving effective clinical outcomes and early recovery. Surgery is one of the treatment strategies for the treatment and management of cancer. Surgery is selected in case the tumor is benign and its complete removal is easy and is not associated with any harm other vital and healthy organs of the body (Perros et al., 2014). Surgical removal of the tumor is associated with certain limitations such as infections at the sites of surgery that can harm the normal tissues and can lead to morbidity and mortality. Moreover, occurrence of surgery associated infections also increases the treatment cost (Johnson et al., 2016). Moreover, the surgery failure can cause recurrence of cancer and metastasis which in turn decreases patient life expectancy by half (Lukianova-Hleb et al., 2016).

Radiotherapy involves the use of radiations and destroys cells by damaging their components. Radiotherapy is preferred for treatment of a local tumor in combination with surgery (Allen et al., 2017; Fournier et al., 2016). It is used when surgery cannot remove the tumor completely and chances of normal tissue damage exist. However, radiotherapy damages healthy cells along with cancerous cells in addition to being time consuming and quite expensive (Tekade et al., 2014). Side effects of radiotherapy include irritation and damage to skin upon repeated exposure to radiation beams. Damage to salivary glands and hair loss most frequently occur in cases of neck and head cancer treatment with radiotherapy (Huang et al., 2015). Immunotherapy involves inducing, enhancing, or suppressing the immune system using various immunological agents (De Vries and Figdor, 2016). It is associated with risks such as swelling, itching, soreness, and redness in the area of administration. Immunological changes can also result in weight gain owing to extra fluids, diarrhea, heart palpitations, and infections. Immunotherapy also affects other vital organs and is considered time consuming (Gotwals et al., 2017). Laser therapy involves penetrating the tumor with laser light and destroying it through increase in temperature. It also causes the tumor to shrink and deprives it of oxygen and nutrition (Rhee et al., 2016). Photodynamic therapy involves a photosensitizing agent that is activated through a specific type of light and kills cancerous cells through a chemical reaction. Cervical, skin, rectum, and colon cancers are treated with laser light. Laser light is also used for the removal of small growths that can result in the development of cancers. Shortcomings associated with laser light include the need to repeat laser light applications over a prolonged period for complete removal of the tumors (Sonis et al., 2016).

Owing to the invasive nature and other problems associated with these cancer treatments, preference has been given to chemotherapy for cancer treatment and management. Chemotherapy involves the systemic administration of anticancer drugs to patients for inhibiting the growth of rapidly growing cancerous cells (Jabir et al., 2012). Rapid division is the main characteristic of cancerous cells destroyed by conventional anticancer drugs given as part of chemotherapy strategy. The combination of chemotherapy with any other treatment strategy is currently preferred for the management and treatment of cancer due to its increased, quick, and positive responses; decreased resistance; and higher tolerability (Xu et al., 2015). Unfortunately, expected clinical outcomes of chemotherapy cannot be achieved due to certain barriers. Physicochemical properties of anticancer drugs such as lower aqueous solubility and permeability result in their inferior clinical outcomes (Thanki et al., 2013). To exert pharmacological action, a sufficient and reproducible amount of a drug should reach the target site, a process that depends on the solubility of the drug in plasma and other physiological fluids (Bhattachar et al., 2006). For a drug to be absorbed, it first has to dissolve in the physiological fluids (Bhattachar et al., 2006). Thus the lower aqueous solubility of most anticancer drugs reduces their therapeutic efficacy, making expected clinical outcomes unachievable. Once a drug has been solubilized, it has to pass through a biological barrier to reach the receptors or site of action. Drug permeability thereby influences the overall pharmacokinetic behavior of the drug. Poor biological membrane permeability of anticancer drugs reduces their biological performance and ultimately their therapeutic efficacy (Shaikh et al., 2012; Sugano, 2011).

Currently used chemotherapeutic agents do not differentiate between normal and cancerous cells and are nonspecific in their action toward cancer cells. This in turn results in side effects on normal cells includi...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Chapter 1. Potential physical and biological barriers leading to failure of cancer chemotherapy
• Chapter 2. Nanotechnological strategies involved in the targeted delivery of anticancer drugs
• Chapter 3. Liposome-based targeted delivery of anticancer drugs for effective therapy of brain tumors
• Chapter 4. Ligand-functionalized nanocarrier-based active drugs targeting for liver cancer therapy
• Chapter 5. Surface-functionalized magnetic nanoparticles in cancer-drug delivery and diagnosis
• Chapter 6. Nanocarrier-based targeted pulmonary delivery: novel approaches for effective lung cancer treatment
• Chapter 7. Enhancing therapeutic efficacy of anticancer drugs through targeting of functionalized niosomes
• Chapter 8. Carbon nanotubes: versatile nanocarriers for effective delivery of anticancer drugs
• Chapter 9. Construction of stimulus-responsive micelles systems for efficient targeting of cancer drugs
• Chapter 10. Nanotargeted radiopharmaceuticals for cancer diagnosis and treatment
• Chapter 11. Potential role of gold nanoparticles in cancer diagnosis and targeted drug delivery
• Index