Nanotechnology: In health and medicine
Nanotechnology is the study of extremely small particles with size ranging from 0.1-100 nm. The term ‘nano’ is derived from a Greek term nanos which means dwarf. A nanometre is a billionth of a metre. It is an emerging field which has caught the fancy of researchers worldwide. Nanotechnology is processing of atoms and molecules to produce miniscule structures with special physicochemical properties such as rigidity, hydrophobicity, size, shape , charge, conductance, chemical reactivity, magnetism. The last decade has seen exponential advancement in this field leading to its utilization in health, medicine, electronics, communication, environment, and energy. Use of nanoparticles for drug delivery, genome sequencing, cancer detection and treatment, repair of tissues and enzymes and better topical drug tolerance has revolutionized the field of health and medicine.
The seed of nanotechnology was sown by physicist Richard Feynman in his talk ‘There’s plenty of room at the bottom’ in 1959 in which he discussed the possibility of synthesis at the atomic level. The term ‘nanotechnology’ was coined by Norio Taguchi in 1974. Another pioneer in the field of nanotechnology is K. Eric Drexler who helped in the development of this concept and also wrote the first book on this concept in 1986 ‘Engines of creation’. The development of scanning tunneling microscope in 1981 enabled visualization of individual atoms and molecules. In 1999 1st book on nanomedicine was published by R. Freitas. National nanotechnology initiative was launched in 2000 by the U.S. government. It is said that the era of nanotechnology began from 2010 and will see groundbreaking revolutions in the next few years in all applied fields. The rapid advancement in nanotechnology in recent years and its vast array of applications has also raised concern over its potential harm and danger. It is speculated that we are advancing this technology at a rate at which it will soon become self-reliant and out of our control. Keeping these controversies in mind there is a call for laws and regulations over its usage.
Manufacturing of nano particles involves 2 approaches:
Top down approach reduces large pieces of materials all the way down to the nanoscale. This approach requires larger amounts of materials and can lead to waste as the excess material is discarded. The bottom-up approach creates products by building them up from atomic- and molecular-scale components, which can be time-consuming but involves less wastage. Scientists are exploring the concept of placing certain molecular-scale components together that will spontaneously “self-assemble,” from the bottom up into ordered structures which are being referred to as nanofactories. These self-reliant, self-assembling independent factories can be utilized in any field reducing labor, time, space and effort.
Nanomaterials can be either nanocrystalline or nano structured material. Nano structures include dendrimers, micelles, drug conjugates, carbon nanotubes, quantum dots, metallic and silica nanoparticles.
Dendrimers: These are hyperbranched tree-like structures and enclose cavities with size less than 10nm. These are used for long targeted delivery of bioactive materials to required sites.
Liposomes: Most developed nano carriers for targeted delivery of drugs due to their small size, 50-200nm. Liposomes possess versatility and biocompatibility. Gene, protein, vaccine, and drugs can all be transported via liposomes.
Inorganic nanoparticles are made of metal (gold or silver), metal oxide (iron), and ceramic material (silica), encapsulating medication in their interior and are especially used as biosensors and treatment of cancer.
Quantum Dots are a nanocrystalline semiconductor material with an exclusive spectroscopy and with optical properties and are good candidates for diagnostic applications.
Carbon nano tubes: These are unique for their size, shape, and have unique physical properties. Nano tubes have some special advantages over other drug delivery and diagnostic systems due to their unique physical properties.
Applications of nanotechnology:
1. Health and medicine
2. Electronics
3. Transport
4. Space exploration
5. Energy and environment.
We will mainly be dealing with the potential and recognised use of nanotechnology in health and medicine with special interest in dermatology.
Nanomedicine is an application of nanotechnology which works in the field of health and medicine. Nano-medicine uses the nano materials, and nano electronic biosensors. Nano medicine has shown many potential uses and is soon going to be indispensable for health and medicinal technology. With the help of nano medicine early detection and prevention, improved diagnosis, proper treatment and follow-up of diseases are possible. Various diseases like metabolic disorders e.g diabetes, skin diseases, cardio vascular diseases, neurodegenerative diseases, inflammatory diseases, infective diseases, genetic disorders malignancies can be diagnosed early and treated with nanoparticles. Nanotechnology can be used for tissue engineering for organ transplantation.
Oncology: Nanotechnology has shown great uses and benefits in the field of diagnosis and treatment of cancer. Due to the small size of nano particles can be of great use in oncology, both in diagnosing and treating malignancies. Nano particles, such as quantum dots, can be used in conjunction with MRI, to produce exceptional images of tumor sites. As compared to organic dyes, nano particles are much brighter and need one light source for excitation. Thus the use of fluorescent quantum dots produce a higher contrast image and at a lower cost than organic dyes used as contrast media.When tagged with antibodies they emit fluorescence that helps in diagnosing tumors. Taking an example of malignant melanoma which is a skin cancer, topical application of quantum dots would allow sentinel lymph node evaluation without disturbing the skin and used as a non-invasive method to evaluate the spread of malignancy.
Nano shells of 120 nm diameter, coated with gold were used to kill cancer tumors in mice. These nano shells are targeted to bond to cancerous cells by conjugating antibodies or peptides to the nano shell surface. Area of the tumor is irradiated with an infrared laser, which heats the gold sufficiently and kills the cancer cells. Nano particles are used in cancer photodynamic therapy, wherein the particle is inserted into the tumor in the body and is illuminated with photo light from the outside. The particle absorbs light and if it is of metal, it will get heated due to energy from the light. High energy oxygen molecules are produced due to light which chemically reacts with and destroys tumors cell, without reacting with other body cells. Photodynamic therapy has gained importance as a noninvasive technique for dealing with tumors.Carbon nano tubes, 0.5–3 nm in diameter and 20–1000 nm length, are used for detection of DNA mutation and for detection of disease protein biomarker.
Stem cell and tissue engineering: Regenerative medicine is another branch which has shown great promise. Nanoparticles both organic and inorganic can be used to bioengineer artificial tissues, enzymes, and genes. Tissues can be controlled at the nanoscale to control cellular activities and tissue formation at the subcellular level.
Drug delivery: Advantages of using nanotechnology as a carrier for different drugs are the site specific drug delivery, lesser side effects, more duration of action of the drug due to sustained release, protecting the therapeutic agent from chemical, physical and biological damage and increased cellular uptake of the drug. Targeted drug delivery will lead to less drug wastage and more cost effectiveness. A drug with poor solubility will be replaced by a drug delivery system, having improved solubility due to the presence of both hydrophilic and hydrophobic environments. Tissue damage by the drug can be prevented with drug delivery, by regulated drug release.Thus variety of nano particles such as dendrimers, liposomes, polymeric nano particles, solid nanoparticles, nano structured lipid particles etc are being used as drug delivery system. Metallic nano particles like iron and gold are being used in cancer therapeutics. They encapsulate the drug and deliver it to the desired site. Drugs which are commonly used nowadays with nanotechnology are analgesics with their sustained release properties , antibiotics covered with polymeric nano particles, cortico-steroids decreasing inflammatory process inside the body, drugs for hair fall , acne treatment , anti-fungals, silver used as an anti bacterial agent in wound dressing and in many agents are being used in many other diseases.
Nano imaging: The use of nano materials as contrast especially gold nano particles and quantom dots has revolutionised diagnostics especially in neurodegenerative diseases and cancer. One of the important uses of nanotechnology is directed towards development of improved diagnostic techniques to screen complex diseases. Screening indicates identification of the cause of illnesses, monitoring the improvement or progression of the state of diseases such as cancer, cardiovascular or neurodegenerative diseases. Nanotechnology enables the manipulation of materials at nanoscale and has shown potential to enhance sensitivity, selectivity and lower the cost of the diagnosis. Several types of nanomaterials such as metals, metal-oxides and quantum dots have shown ample advantages over traditional diagnosis. Nanotechnology has also opened several avenues which could be further developed to enable enhanced visualization of tissues, cells, DNA and proteins over a point-of-care device. Quantum Dots may be used in the future for locating tumors in patients and in the near term for performing diagnostic tests in samples. Gold nanoparticles, in combination with fluorescent protein, is being used in diagnosis of cancer by emitting fluoroscence when binding occur with the target atypical cell. Carbon nanotubes are specialised structures having good conductivity with special property of alteration in their conductivity on binding to macromolecules like nucleic acids and antibodies, their conductivity changes. They are used in diagnosis of skin infection and malignancies. Iron oxide nanoparticles can used to improve MRI images . The magnetic property of iron oxide enhances the images from the Magnetic Resonance Imagining scan.
Neurodegenerative disorders: One of the most important applications of nanotechnology is in the treatment of neuro degenerative disorders .Aim of nanotechnology is regeneration and neuro protection of the central nervous system (CNS). Nanotechnology could provide devices to limit and reverse neuro pathological disease states, to support and promote functional regeneration of damaged neurons, to provide neuro protection and to facilitate the delivery of drugs and small molecules across the blood–brain barrier. Potential for use has been cited in Alzheimer's disease, Parkinson’s disease, acute ischaemic stroke and tubercular menigitis. Nanomaterials are being used for dissolving clots and repairing afected vessels in ischaemic and embolic episodes.
Gene silencers : Gene silencing is currently one of the most promising new approaches for disease therapy in genetically inherited disesases or diseases occuring due to mutations.Small interfering RNA (siRNA), showed significant potential in new molecular approaches to down-regulate specific gene expression in mammalian cells.However, RNAs cannot easily penetrate cell membranes. Small interfering ribonucleic acids encapsulated with polymeric nanoparticles can precisely inactivate the gene expression
Vaccine Delivery: Conventional vaccines have concerns about the weak immunogenicity of these vaccines, intrinsic instability , toxicity, and multiple administrations. Recently nanotechnology have been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the immune responses. Nanoparticles have been used to improve the cellular uptake of antigens, thereby increasing antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. Nanocarrier-based vaccine delivery systems, with liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials are used.. Micro needle patches engineered with topical vaccines are delivered to the skin avoiding invasive methods of vaccination.
Nanotechnology in dermatology: Nanomaterials and nanobiotechnology have the potential to dramatically alter the field of cosmeceuticals. Nanoparticles can encapsulate a vast range of substances for both pharmaceutical and cosmetic use. They are applied over the skin and these agents enter either through the the stratum corneum or through the hair follicles.
1. Sunscreens is one of the most commonly used over the counter drugs. Nanoparticles of titanium dioxide and zinc oxide are used in sunscreens which increases the efficacy and making them more cosmetically elegant as by decreasing the white effect remain after using the conventional ones and decreases their stickyness and covering the skin more evenly. Utilization of nanoparticles in sunscreen is approved by FDA in 1990.
2.Use of nanoparticles in moisturisers increases their permeation into skin. Nanoparticles enable transport of natural fatty acids like ceramides with large molecular structure deeply in the skin in patients with barrier defects like atopic dermatitis.
3.Botulinum toxin and hyaluronic acid are anti wrinkle agents that were till recent available only as injectables, which was painful, tedious and costly. Hyaluronic acid in its bulk form is 50,000 nm or larger in size and is unable to penetrate skin when applied topically and hence fillers have been injected to penetrate the skin. Nanosized particles of hyaluronic acid can penetrate the skin and many such topical fillers are being introduced in the market. Botulinum toxin has been stabilized and encapsulated in a form that allows penetration of the skin and apparent effacement of rhytides in early clinical trials.
4.Chitin nanofibrils are made from a polysaccharide obtained from crustacean shells. It is easily metabolised by endogenous body enzymes, and is eco and bio compatible. These nanofibrils activate keratinocyte and fibroblast proliferation and regulate collagen synthesis. There is interesting evidence in relation to their capacityto not just act on the appearance of photoaged skin, but also to promote wound healing (Chitomesh®).
5.Chlorhexidine gluconate carried by nanoparticles (Nanochlorex®) is having an immediate antibacterial effect, due to fast absorption from the capsule wall, and a prolonged effect due to sustained liberation from the nanoparticle.
6.The most commercialised antibacterial nanomaterial is nanosilver, used in wound and burn dressings. Silver nanoparticles act as antibacterials against mainly gram negative bacteria by physicaaly binding to cell wall and causing cell lysis. Besides this silver ions have been shown to alter cell’s electrochemical structure causing further bactericidal effects. The various methods of antibacterial resistance have not shown effectiveness against silver nanoparticles.
7.Use of nanovesicles and encapsulated liposomes are being used for increased delivery of cosmeceuticals and drugs into the skin. Liposomal amphotericin B, methotrexate, cyclosporine and podophyllotoxin have shown great promise. These drug carriers help in crossing the skin’s horny layer for better effect with improved tolerability. The recent incorporation of retinoids in liposomes have lead to their improved tolerability and increased usage. Similarly liposomal antifungals and corticosteroids have lead to sustained drug levels, increased tolerance, lesser dosage and minimal side effects.
8.Photodynamic therapy using gold particles is being used for sentinel node evaluation and targeted cell killing. Using nanoparticles to selectively label cancer cells targeted killing can be done without systemic side effects. Combining nanoparticles with many anticancer drugs have lead to their improved effects and tolerability.
9.Medicated textiles using nanoparticles having anti-bacterial properties are under development.
Risk factors associated with nanotechnology :
With the innumerable benefits, comes the risks. No technology no change comes without side effects and nanotechnology is no different. Nanoparticles like single –celled organisms and inorganic nano materials like volcanic ash have been present in the enviroment since times immemorial without any side effects. But we are daily adding waste man-made nanoparticles into the environment daily without any concern about the associated pollution. Nanopollution is the study of pollutant effects associated with nanoparticles. To date no significant reports have come up on the above subject and though debatable, its relevance cannot be ignored. In our body, non-biodegradable nanoparticles can get accumulated & act as a foriegn body leading to granuloma formation , hardening of organs known as scleromyxedema and can be potentially teratogenic and mutagenic. Due to their shrunken size there is an increased proportion of surface area to volume ratio per unit mass due to which reactivity of each nano particle increases & it has been postulated that nanoparticles can elicit haptens or cross reactant leading to allergic reactions. Sunscreens containing nano Titanium dioxide particles has an oxidising property which can generate free radicals to cause damage to the cells by damaging DNA, RNA and cell membrane. Besides this the materials constituting nanoparticles like quantum dots are potentially toxic and their long term effects are still under study.
Conclusion: Nanotechnology is the beginning of an era in which nanorobots and nanoparticles will soon find, repair and cure diseases, modulate environment, form self assembling and self reliant manufacturing units. The possibility of its uses and implications are enormous. In the last decade there has been a boom in studies pertaining to nanotechnological advancement in many fields. But great advancement always comes at a price and in this case, we still don’t know the exact price we will have to pay in the coming future. Keeping this in mind, advancements and uses of this field should be cautious, carefully monitored and kept in check from going in the wrong hands.
