Biomedical Applications of Nano-materials, Study Guides, Projects, Research of Nanotechnology

Download Biomedical Applications of Nano-materials and more Study Guides, Projects, Research Nanotechnology in PDF only on Docsity! BIOMEDICAL APPLICATIONS OF NANOMATERIALS AYESHA TARIQ AREEBA SIDDIQUE SHANZA TARIQ KHWAJA FAREED UNIVERSITY OF ENGINEERING AND INFORMATION TECHNOLOGY, RAHIM YAR KHAN. SUMMARY Research and development of biomedical applications of nanomaterials is becoming the most extensively studied discipline because the easy, rapid, low- cost, highly sensitive, and highly selective nanomaterials contribute to advances in next generation medicines. The advances in surface chemistry provide a variety of new methods for designing target molecule recognition systems. Furthermore, the advances in nanofabrication technologies promise not only construction of novel transducers but also miniaturization and integration of biosensors with high throughput. Nanoparticles are used in biomedical applications as they offer many advantages to larger particles such as increased surface to volume ratio and increased magnetic properties. Nanoparticles may be classified into different Nano-systems. Nano-particles can be divided into four Nano-systems; metallic nanoparticles, bimetallic or alloy nanoparticles, metal oxide nanoparticles and magnetic nanoparticles. 1. Introduction Nanoparticles are defined as ‘solid colloidal particles ranging in size from 10 to 1000 nm (1 μm)’. They can possess physical properties such as uniformity, conductance or special optical properties that make them desirable in materials science and biology. Nanomedicine is the branch of medicine that utilizes the science of nanotechnology in the preclusion and cure of various diseases using the nanoscale materials, such as biocompatible nanoparticles and nanorobots, for various applications including, diagnosis, delivery, sensory, or actuation purposes in a living organism. In recent years, there has been a steadily growing interest in using these Nano systems in different biomedical applications such as targeted drug delivery, hyperthermia, photoablation therapy, bioimaging and biosensors. A lot of literature have focused on iron oxide nanoparticles because of their superior chemical, biological and magnetic properties including chemical stability, non-toxicity, biocompatibility, high saturation magnetisation and high magnetic susceptibility. This review investigates other Nano systems such as metallic nanoparticles like gold (Au) and silver(Ag), bimetallic nanoparticles like iron cobalt (Fe–Co) and iron platinum (Fe–Pt) and metal oxides including titanium dioxide (TiO2), cerium dioxide (CeO2), silica (SiO2) and zinc oxide (ZnO) for possible use in biomedical applications. Nanoparticles are used in biomedical applications as they offer many advantages to larger particles such as increased surface to volume ratio and increased magnetic properties. Nanoparticles may be classified into different Nano-systems. Nano-particles can be divided into four Nano-systems; metallic nanoparticles, bimetallic or alloy nanoparticles, metal oxide nanoparticles and magnetic nanoparticles. 2. Classification of Nano-systems In this section, we will classify nanoparticles into different Nano-systems; metallic nanoparticles, bimetallic or alloy nanoparticles, metal oxide nanoparticles and magnetic nanoparticles. The list of metallic nanoparticles includes gold and silver. The bimetallic list includes Fe–Co, Fe–Ni, Fe–Cu, Cu–Ni and Fe–Pt nanoparticles. The metal oxide nanoparticles consist of TiO2 , CeO2 , SiO2 and ZnO. Magnetic nanoparticles are comprised of Fe3-O4 , Co–Fe2-O4 and Mn–Fe2-O4 . These nanoparticles are the most investigated as they all possess unique properties that are essential for use in different biomedical applications. 2.1. Magnetic nanoparticles Magnetic nanoparticles are a class of nanoparticle that can be manipulated using magnetic fields. Such particles commonly consist of two components, a magnetic material, often iron, nickel and cobalt, and a chemical component that has functionality. Iron oxide nanoparticles are the most researched and commonly used materials for biomedical applications. Its popularity is due to unique chemical, biological and magnetic properties such as chemical stability (Tendency of a material to resist change or decomposition due to internal reaction, or due to the action of air, heat, light, pressure, etc.), non-toxicity (The state or condition of being nontoxic.), biocompatibility (Biocompatibility is an ability of a material to perform its desired function without causing any local or systemic adverse response in the recipient of the material.), high saturation magnetization ( It is the state reached when an increase in applied external magnetic field H cannot increase the magnetization of the material further.) and high magnetic susceptibility (Magnetic susceptibility is the degree to which a material can be magnetized in an external magnetic field.). Iron oxide has different oxidation states including iron (II) oxide (Fe-O), iron (III) oxide (Fe2-O3) and iron (II, III) oxide (Fe ). Iron (III) oxide (Fe ) has different crystalline polymorphs α-Fe2-O3 , β-Fe2-O3 , γ-Fe2-O3 and ε-Fe2-O3 . It was found that maghemite (γ- Fe2-O3) and magnetite (Fe3-O4 ) are the most biocompatible but magnetite (Fe ) is the most commonly used form for biomedical applications. However, this form of iron oxide has a tendency to oxidise so coating with a biocompatible shell is required. Some examples of coatings include polymers, ceramics and metals. The magnetic properties of iron oxide nanoparticles can be improved by doping with magnetically susceptible elements such as manganese (Mn), cobalt (Co) and nickel (Ni) [103]. Cobalt and Manganese doped ferrites are the most promising for use in biomedical applications. Co-Fe2-O4 nanoparticles have high magneto-crystalline anisotropy, high coercivity, high Curie temperature, moderate magnetisation saturation and are chemically stable. These nanoparticles have been investigated for possible use in magnetic hyperthermia and as contrast agents for MRI. MnFe2-O4 nanoparticles were found to have high magnetisation, magnetic susceptibility and large relativities and were biocompatible. MnFe2- O4 nanoparticles have been researched for possible use in magnetic hyperthermia and as possible contrast agents for MRI. 2.2. Metallic nanoparticles Metal nanoparticles are submicron scale entities made of pure metals (e.g., gold, platinum, silver, titanium, zinc, cerium, iron, and thallium) or their compounds (e.g., oxides, hydroxides, sulfides, phosphates, fluorides, and chlorides). Gold and its compounds have been used for medicinal purposes since its discovery over 5000 years ago. Gold nanoparticles use in biomedical applications is one of the most researched areas. Metallic nanoparticles such as gold (Au) possess unique electronic and optical properties as well as chemical inertness (An inert chemical is one that is stable and unreactive under specified conditions.) and its ability for surface functionalization (Surface functionalization is an effective and often simpler way of altering the surface properties of a material or device to achieve specific goals such as inducing a desired bio-response or inhibiting a potentially adverse reaction.) which is due to the negative charge on its surface. Gold’s unique electronic and optical properties have resulted in its use in biosensors and bioimaging as well as photothermal therapy. Gold’s ease at functionalisation with organic molecules allows for conjugation with ligands (Ligands are ions or neutral molecules that bond to a central metal atom or ion. ), antibodies (An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.) for active or passive drug delivery. Gold’s chemical inertness allows for good biocompatibility in vitro(It refers to the technique of performing a given procedure in a controlled environment outside of a living organism.) and in vivo (in which the effects of various biological entities are tested on whole, living organisms or Figure SEQ Figure \* ARABIC 1: Schematic showing biomedical applications of nanoparticles. 2.6. Targeted drug delivery Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. There are two ways through which nanostructures deliver drugs: passive and self-delivery. In the former, drugs are incorporated in the inner cavity of the structure mainly via the hydrophobic effect. When the nanostructure materials are targeted to a particular sites, the intended amount of the drug is released because of the low content of the drugs which is encapsulated in a hydrophobic environment. Conversely, in the latter, the drugs intended for release are directly conjugated to the carrier nanostructure material for easy delivery. In this approach, the timing of release is crucial as the drug will not reach the target site and it dissociates from the carrier very quickly, and conversely, its bioactivity and efficacy will be decreased if it is released from its nanocarrier system at the right time. Chemotherapy depends on the circulatory system to transport anticancer drugs to the tumour. There are negative side effects of this treatment such as non-specificity and toxicity of the drug, whereby the drugs attack healthy cells and organs as well as the cancerous cells. Therefore, targeted drug delivery is being developed as one alternative to chemotherapy treatment. The aim of targeted drug delivery is to direct the drug to the specific area where the tumour is located and thereby increasing the amount of drug delivered at the tumour site and reducing the side effects. In targeted drug delivery, magnetic nanoparticles are used to deliver the drug to its specific location. Generally, the magnetic nanoparticles are coated with a biocompatible layer, such as gold or polymers, this is done to functionalise the nanoparticles so that the anticancer drug can either be conjugated to the surface or encapsulated in the nanoparticle. Once the drug/nanoparticle complex is administered, an external magnetic field is used to guide the complex to the specific tumour site. The drug is released by enzyme activity or by changes in pH, temperature or osmolality. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. For example, by avoiding the host's defence mechanisms and inhibiting non-specific distribution in the liver and spleen, a system can reach the intended site of action in higher concentrations. Targeted delivery is believed to improve efficacy while reducing side-effects. Figure SEQ Figure \* ARABIC 2: Mechanism for controlled release of drug using different types of nanocarriers. 2.7. Magnetic hyperthermia Hyperthermia therapy is a type of medical treatment in which body tissue is exposed to higher temperatures in an effort to treat Lyme disease and cancer. Hyperthermia is a therapeutic technique whereby heat is applied to destroy cancerous cells and tissue. The temperature of the infected or diseased area is raised to 41–46 °C to kill the cancerous cells without damaging the healthy cells. Cancerous cells have a higher sensitivity to temperature than healthy cells. Cell apoptosis will occur when the cancerous cells are heated to 41–46 °C, this is called hyperthermic effect. Necrosis will occur if the cells are heated to above 46–48 °C, referred to as thermoablation. Hyperthermia treatment is used in combination with radiotherapy and chemotherapy to treat cancerous cells. There are three different types of hyperthermia treatment local (Local hyperthermia heats a very small area and is typically used for cancers near or on the skin or near natural openings in the body e.g., the mouth. In some instances, the goal is to kill the tumour by heating it, without damaging anything else. The heat may be created with microwave, radiofrequency, ultrasound energy or using magnetic hyperthermia (also known as magnetic fluid hyperthermia)), regional (Regional hyperthermia heats a larger part of the body, such as an entire organ or limb. Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications) and whole body hyperthermia (Whole-body hyperthermia heats the entire body to temperatures of about 39 to 43 °C (102 to 109 °F), with some advocating even higher temperatures. It is typically used to treat metastatic cancer (cancer that spread to many parts of the body)). In local hyperthermia treatment, heat is applied to a small area which can be done using different techniques such as radio frequency, microwave and ultrasound. These methods are used to supply energy to raise the temperature of the tumour. Magnetic nanoparticles can also be used in local hyperthermia treatment. Regional hyperthermia is generally used to treat large tissue areas. In this treatment, external devices are used to heat an organ or limb. Whole body hyperthermia is often used to treat metastatic cancer that has spreads throughout the body. Local hyperthermia treatment is the main type of hyperthermia that will be discussed here. For local hyperthermia treatment, magnetic nanoparticles can be delivered to the tumour in four possible ways arterial injection, direct injection, in situ implant formation and active targeting. Arterial injection requires injecting the fluid containing the magnetic nanoparticles into the tumours arterial supply. Direct injection involves directly injecting the fluid containing the magnetic particles into the tumour this method is the most commonly used. In situ implant formation entails using injectable formulations that form gels such as hydrogels (chitosan and sodium alginate) and organogels (Poly (ethylene-co-vinyl alcohol and cellulose acetate) to entrap magnetic particles into tumours. Active targeting is another method of delivering magnetic nanoparticles to the tumour site. It generally involves coating the magnetic nanoparticles with a tumour-specific antibody and injecting into the bloodstream. The antibodies are tumour specific and will bind to the target site. Magnetic fluid hyperthermia is based on the principle of converting electromagnetic energy into heat. The magnetic nanoparticles are distributed around the target site and an alternating magnetic field is applied. This alternating magnetic field supplies energy which helps the magnetic moments in the particles to overcome the reorientation energy barrier. Energy is dissipated when the moments in the particles relax to an equilibrium state. This then results in the heating of the particles by Brownian rotation or Neel relaxation. Brownian rotation is a result of rotation of the nanoparticles and is defined by: where is the Brownian relaxation time, η is the viscosity, is the hydrodynamic volume of the particle, k is Boltzmann constant and T is temperature. Neel relaxation is a result of rotation of magnetic moments within the nanoparticles and is defined by: where is the Neel relaxation time, is 10 seconds, e is anisotropy constant 0 −9 K and VM is the volume of the particle. If both relaxations occur at the same time this is defined by: τ is the relaxation time if both effects occur at the same time. The relaxation times are dependent on the nanoparticles size, the larger the particles the larger the Brownian and Neel relaxation time constant will be. The heat generated by magnetic nanoparticles is quantized in terms of specific absorption rate (SAR): where C is the specific heat capacity of the sample and ΔT/Δt is the rate of temperature increase. 2.8. Bioimaging Figure SEQ Figure \* ARABIC 3 Photothermal therapy. Figure SEQ Figure \* ARABIC 4 Photodynamic therapy. 2.10. Biosensors Biosensors are defined by IUPAC as integrated receptor–transducer devices, which are able to provide selective quantitative or semi-quantitative analytical information using a biological recognition element. A biosensor is an analytical device that is used for analysing biological samples. It converts a chemical, biological or biochemical response into an electrical signal. A biosensor contains three essential components (1) bioelement or bioreceptor, which are generally made up of enzymes, nucleic acids, antibodies, cells or tissues (2) the transducer which can be electrochemical, optical, electronic, piezoelectric, pyroelectric or gravimetric and (3) the electronic unit which contains the amplifier, processor and display. Figure SEQ Figure \* ARABIC 5: Schematic of a biosensor. The bioreceptor recognises the target analyte/substrate of interest, the transducer then transforms the resulting signal into an electrical signal that is more easily quantified. Figure SEQ Figure \* ARABIC 6: Pictorial representation of different steps involved in signal processing of biosensor. Nanoparticles can be used as bioreceptors once coated with a bioresponsive shell. Biosensors are utilised in many different areas including environmental, bio/pharmaceutical, food and medical industries A typical biosensor is composed of three main parts the electronic system, which contains the signal amplifier, processor and display unit, the transducer, which converts the reaction of the sample analyte and bioreceptor into an electrical signal and a bioreceptor, which is composed of a biological substance which targets and or binds to a specific compound. The transducer used in the biosensor depends on the reaction that is generated between the sample and the bioreceptor. Electrochemical biosensors such as amperometric sensors detect changes in current due to oxidation/reduction reactions. Potentiometric sensors can detect changes in charge distribution. Optical biosensors can be colorimetric which detect changes in light adsorption or photometric which detect changes in photon output. Piezoelectric sensors can detect changes in mass. Conclusion In this review, we discussed about the nanomaterials, its basic types and mainly biomedical application of nanomaterials. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. . The current review, presents an updated summary of recent advances in the field of nanomedicines and Nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. nanobiotechnology focuses on the ability to work at the molecular and atomic level to fabricate structures combining biological materials and synthetic materials, taking into account engineering, physics, chemistry, genomics and proteomics. References 1. del_Pino P, Pelaz B (2012) Hyperthermia using inorganic nanoparticles. In: Fuente JMdl, Grazu V (eds) Nanobiotechnology: inorganic nanoparticles versus organic nanoparticles: Frontiers of nanoscience, vol. 4. Elsevier, Amsterdam, The Netherlands, pp 309–335 CrossRef Google Scholar 2. Marciello M, Luengo Y, P. 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