Nanoparticle-Based Drug Delivery in Cancer Treatment

Loutfy H. Madkour

• Publisher: CRC Press
• Year: 2022
• ISBN:
  9781000532180
• Edition: 1
• Topic: Sciences physiques
• Subtopic: Nanotechnologie

The careful choice of nanoparticles as targets and in drug delivery routes enhances therapeutic efficacy in cancer. Nanoparticle-Based Drug Delivery in Cancer Treatment discusses nanotechnological developments of interfering RNA-based nanoparticles, delivery vehicles, and validated therapeutic RNAi–molecular target interactions and explains the results of clinical and preclinical trials. The book also gives strategies for universal methods of constructing hybrid organic–inorganic nanomaterials that can be widely applied in the biomedical field.

Key Features:

• Reviews recent advances of nanoparticle-mediated siRNA delivery systems and their application in clinical trials for cancer therapy

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• Focuses on material platforms that establish NPs and both localized and controlled gene silencing

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• Emphasizes the most promising systems for clinical application

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• Surveys progress in nanoparticle-based nanomedicine in cancer treatment

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• Describes the most advanced of the nonviral nanocarriers for delivery of oligonucleotides to malignant blood cancer cells

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This book is a valuable resource for researchers, professors, and students researching drug delivery, gene carriers, cancer therapy, nanotechnology, and nanomaterials.

1 The Advantages and Versatility of Carrier-Free Nanodrug and Nanoparticle Systems for Cancer Therapy

DOI: 10.1201/9781003229674-1

1.1 Nanoparticles' (NPs) Fabrication and Their Applications in Cancer Treatment

Current cancer treatments include surgical intervention, radiation, and chemotherapeutic drugs, which often also kill healthy cells and cause toxicity to the patient. Conventional chemotherapeutic agents also do not show targeted action and are distributed nonspecifically in the body where they affect both cancerous and normal cells, thereby limiting the dose achievable within the tumor cells and also resulting in suboptimal treatment due to excessive toxicities.

Nanotechnology is the science of nanoscale, which is the scale of nanometers or one-billionth of a meter. Nanotechnology encompasses a broad range of technologies, materials, and manufacturing processes that are used to design and/or enhance many products, including medicinal products.

Green synthesis of nanoparticles (NPs) [1] is a global eco-friendly method to develop and produce nanomaterials with unique biological, physical, and chemical properties. This technology has achieved considerable progress in the oncology field in recent years. Recently, attention has shifted toward biological synthesis, owing to the disadvantages of physical and chemical synthesis, which include toxic yields, time and energy consumption, and high cost. Many natural sources are used in green fabrication processes, including yeasts, plants, fungi, actinomycetes, algae, and cyanobacteria. Cyanobacteria are among the most beneficial natural candidates used in the biosynthesis of NPs, due to their ability to accumulate heavy metals from their environment. They also contain a variety of bioactive compounds, such as pigments and enzymes, which may act as reducing and stabilizing agents. Cyanobacteria-mediated NPs have potential antibacterial, antifungal, antialgal, anticancer, and photocatalytic activities.

Most chemotherapeutic agents are not specific to the cancer cells they are intended to treat, and they can harm healthy cells, leading to numerous adverse effects. Due to this nonspecific targeting, it is not feasible to administer high doses that may harm healthy cells. Moreover, low doses can cause cancer cells to acquire resistance, thus making them hard to kill. A solution that could potentially enhance drug targeting and delivery lies in understanding the complexity of nanotechnology. Engineering pharmaceutical and natural products into nanoproducts can enhance the diagnosis and treatment of cancer. Novel nanoformulations such as liposomes, polymeric micelles, dendrimers, quantum dots (QDs), nanosuspensions, and gold nanoparticles (Au-NPs) have been shown to enhance the delivery of drugs. Improved delivery of chemotherapeutic agents targets cancer cells rather than healthy cells, thereby preventing undesirable side effects and decreasing chemotherapeutic drug resistance. Nanotechnology has also revolutionized cancer diagnosis by using nanotechnology-based imaging contrast agents that can specifically target and therefore enhance tumor detection. In addition to the delivery of drugs, nanotechnology can be used to deliver nutraceuticals like phytochemicals that have multiple properties, such as antioxidant activity, that protect cells from oxidative damage and reduce the risk of cancer. There have been multiple advancements and implications for the use of nanotechnology to enhance the delivery of both pharmaceutical and nutraceutical products in cancer prevention, diagnosis, and treatment [1].

Nanotechnology is an emerging field that includes synthesis, characterization, and development of various nanomaterials [2,3] that have significant roles in daily life, providing valuable products that improve industrial production, agriculture, communication, and medicine [4]. Currently, around 1000 commercial nanoproducts are available in world markets [5,6]. The term “nano” denotes any particles or materials with at least one nanosized (1–100 nm) dimension. NPs differ significantly from their bulk materials in terms of physical, chemical, and biological properties [7]. These differences are mainly due to their high surface area-to-volume ratio, which results in considerable differences in catalytic and thermal activities, melting point, conductivity, mechanical properties, and optical absorption. These properties make NPs applicable in almost all fields [8].

NPs have significant roles in bio-diagnostic and optical biosensing, nanophotonics, and imaging and treatment of many diseases affecting human health [9]. Silver nanoparticles (Ag-NPs) can interact effectively with microbe surfaces due to their small size and large surface area and are thus used as antimicrobial agents [10]. Ag-NPs synthesized using Fusarium keratoplasticum and embedded in cotton fiber showed significant antibacterial activity against pathogenic bacteria [11]. Carbon nanotubes (CNTs) have a key role in drug delivery, because of their capacity to carry drugs and control their release into target cells [12]. QD NPs have been used to detect the location of malignant cells inside the body [13]. Iron oxide NPs are used in resonance imaging and diagnosis of tumors [14]. Au-NPs are in high demand for various applications in multiple fields owing to their low toxicity [15]. In addition, Au-NPs have high photothermal and photoacoustic activity, making them suitable for use in photothermal therapy (PTT) for cancer. Other biogenic NPs such as copper oxide NPs [16], zinc oxide NPs [17], selenium NPs [18] acted as potent anticancer agents. The variation in NP shapes, including spherical, cubic, needles, triangular, and rod, enables them to be used in diverse areas such as device manufacture, electronics, optics, and biofuel cells (Figure 1.1) [19].

FIGURE 1.1 Various shapes of nanoparticles.

The physicochemical routes used to produce NPs are often unwieldy and expensive and result in liberation of toxic byproducts that threaten ecological systems [20]. To avoid these drawbacks, green synthesis of NPs using biogenic agents has become an alternative to chemical and physical synthesis [21]. Diatoms, mushrooms, algae, plants, fungi, bacteria, actinomycetes, lichen, cyanobacteria, and microalgae have been shown to successfully reduce metal precursors to their corresponding NPs [22]. Intra- and extracellular green synthesis techniques have been developed to reduce bulk materials to nanoforms using biological extracts [23]. These nanomaterials can be synthesized in the presence of biocompounds such as flavanones, amides, enzymes, proteins, pigments, polysaccharides, phenolics, terpenoids, or alkaloids, to aid the reduction and stabilization of NPs [22]. A high surface area-to-volume ratio is the target physical feature of NPs, as it confers their versatile applicability and ability to withstand harsh conditions [24]. The shape and size of NPs synthesized by microorganisms can be controlled by various abiotic and biotic factors, including pH, temperature, the nature of the microorganisms, their biochemical activity, and interactions with heavy metals [25,26 and 27].

In the past few years, the synthesis of NPs using cyanobacteria has become an active research field [25,28]. Cyanobacteria are a diverse group of photoautotrophic prokaryotes that exist in a wide range of ecosystems [29]. They are distinguished by their ability to fix atmospheric nitrogen (N₂) by reducing nitrogen gas to ammonia using nitrogen reductase enzymes. This is a significant advantage in their role in biotransformation of metals to NPs [20], as they possess the ability to eliminate heavy metal ions from their surrounding environment. Furthermore, they contain various biomolecules including secondary metabolites, proteins, enzymes, and pigments that confer important biological properties such as antimicrobial and anticancer activity [28,30,31]. In addition to these features, cyanobacteria have a high growth rate that facilitates high biomass production. Thus, they represent important nanotechnology-mediated microorganisms that can act as nanobiofactories for NPs [32,33]. Although there have been several detailed reviews of biological synthesis using microorganisms, few studies have focused on synthesis of NPs using cyanobacteria.

1.2 Classification of NPs

NPs can be classified according to various factors, such as shape and dimension, phase compositions, nature, and origin (Figure 1.2) [34]. For instance, natural NPs include those that exist in the biosphere as a result o...