Recent Advances in Pediatrics (Volume 20: Hot Topics) Suraj Gupte, Shamma-Bakshi Gupte
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1GENERAL PEDIATRICS2

Nanomedicine1

OP Mishra
Rajniti Prasad
Utpal Kant Singh
Amanpreet Sethi
 
INTRODUCTION
Like primitive engineers faced with advanced technology, medicine must ‘catch up’ with the technology of human body before it can become really effective. Since the human body is basically an extremely complex system of interacting molecules (i.e. a molecular machine), the technology required to truly understand and repair the body is the molecular machine technology—nanotechnology. A natural consequence of this technology will be the ability to analyze and repair the human body as completely and effectively as we can repair any conventional machine today.1,2
 
Definition of Various Terms2
  1. Nanotechnology is defined as research and technology development at the atomic, molecular or macromolecular levels in the length scale of approximately one to several hundred nanometers.
  2. Nanobiotechnology plays an important role in the discovery of biomarkers and molecular diagnosis and facilitates the integration of diagnosis and therapy.
  3. Nanomedicine is defined as the application of nanobiotechnology in medicine to improve diagnosis as well as therapy.
    It exploits the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale. Nanomedicine has potential impact on the prevention, early and reliable diagnosis and treatment of previously uncurable diseases.
  4. Nanopharmaceutical is defined as the application of nanotechnologies to improve drug discovery and drug delivery.
The relationship of biotechnology, nanotechnology and medicine is mentioned in Figure 1-1.4
zoom view
Figure 1-1: Relationship of biotechnology, nanotechnology and medicine
 
Nanoscale Particles in Human Body and in Use2
  • 25 nm: Microtubule width
  • 15 nm: Antibodies (IgG)
  • 1–20 nm: Most proteins
  • 10 nm (10–8m): Intermediate Filaments (Vimentin)
  • 2–4 nm: Ribosome
  • 2.4 nm: DNA width
  • 1.2 nm: Amino acid (tryptophan)
  • 1 nm: Aspirin molecule
  • 0.2 nm: Individual atom.
 
ORIGIN OF NANOMATERIALS
There are two approaches for the manufacturing of nanomaterials2:
  1. The top-down approach: It involves the breaking down of large pieces of material to generate the required nanostructures from them. This method is particularly suitable for making interconnected and integrated structures such as in electronic circuit, e.g. Carbon based nanomaterials like Graphene, Carbon nanotubes, nanodiamonds, etc.
  2. The bottom-up approach: In this approach single atom and molecule are assembled into larger nanostructures. This is a very powerful method of creating identical structures with atomic precision, although to date, the man-made materials generated in this way are still much simpler 5than nature's complex structures, e.g. Metallic nanoparticles, Gold, Silver, Iron based nanomaterials, etc.
 
PROPERTIES OF NANOMATERIALS
Nanomaterials have the structural features in between of those of atoms and the bulk materials. While most microstructured materials have similar properties to the corresponding bulk materials, the properties of materials with nanometer dimensions are significantly different from those of atoms and bulks materials. This is mainly due to the nanometer size, which render them large fraction of surface, high surface energy, spatial confinement and reduced imperfections, which do not exist in the corresponding bulk materials. Due to their small dimensions, nanomaterials have extremely large surface area to volume ratio, which makes a large fraction of atoms of the materials to be the surface or interfacial atoms, resulting in more “surface” dependent material properties.2,3
 
NANOMATERIALS
 
Carbon Nanomaterials
  1. Carbon nanotubes (single- and multi-walled) are used in AFM, DNA filled and DNA-covered nanotubes for gene therapy, due to their high electric conductivity. It can be used in production of X-ray radiations used in medical diagnosis.
  2. Fullerenes (multi-atomic carbon particles, e.g. C60): Animal experiments revealed that fullerenes and their derivatives could repair damages originating as the result of oxidative processes in the cell. Employment of fullerenes in biological and medical studies is based on their unique physico-chemical properties. C-60 holds a leading position in studies of fullerenes and their derivatives.
In human hepatoma cells, Hep 3B carboxyfullerene C(60) inhibit TGF-beta induced apoptosis due to interaction with oxygen radicals formed in membrane. The presence of carboxyfullerene C-60 prevent UV-induced apoptosis of human keratinocytes. A unique property of fullerene and its derivatives are its ability to penetrate blood-brain barrier. Thus it can be used for treatment of acute and chronic neurodegenerative diseases such as Parkinson's disease.
For penetration inside cells, viruses use receptors located on membrane. Conformation changes of such receptors or their mechanical blockade by interaction of the C(60) fullerene molecule with ideal spherical structure and the size (0.7 nm) will complicate penetration of viral particle inside the cell. Fullerene C (60) with polyvinylpyrrolidone effectively inhibited replication of the influenza virus in experiments on chicken embryos and canine kidney cells. Advantages over Rimantadine (traditionally used drug 6in Influenza) include low dose, more effective and effective over the whole period of viral replication cycle as compared to Rimantadine which is active only in the early part of replication cycle.
Antiviral activity of fullerene C(60) derivatives was also demonstrated for cytomegalovirus, vesicular stomatitis virus and hepatitis C virus. A recent research using computer modelling based on X-ray data, it was demonstrated that Fullerenes C-60 is complimentary to active site of HIV-protease. This inactivates the enzyme and therefore interrupts the viral replication cycle. Carboxyfullerenes was also found effective against streptococcal infection. Positively charged derivatives of Fullerenes inhibited the growth of Mycobacterium tuberculosis.
 
Polymer Based Transport System
Polymer nanoparticles (e.g. polystyrene) are versatile, relatively safe and can be visualized (fluorescently doped), but hard to achieve homogenous size and shape below 10 nm. Polymer based nanoparticles exhibits better stability in biological body fluids and storage but due to their propensity to cause allergic reaction, they are less used. But new biodegradable polymers based on Polylactate (PLA), Polyactidecoglycolide (DL-PLGA) are being developed, which can be effectively employed for transport of various lipophilic preparations such as lidocaine, cyclosporin and tamoxifin.3
Polymer based products and its applications
Product
Application
Genexol PM
Non-small cell lung cancer
Estrasorb
Estrogen therapy
Flucide
Anti-influenza
Basulin
Long-acting insulin
DO/NDR/O2
Paclitaxel delivery
 
Semiconductor Nanoparticles (Nanocrystals) of CdTe, CdSe/ZnS
These particles produce stable fluorescence at multiple wave length, including at widely used excitation at 488 and 568 nm. Their emission wavelengths are tunable by particle size. They can be coupled to bio-molecules for cell imaging and targeted drug delivery. They are very useful as fluorescent probes, but some are very toxic.
 
Quantum Dots
The quantum dots are semiconductor nanocrystals (2–100 nm) with unique optical and electric properties. Quantum dots used for biomedical studies 7represent nanocrystals with a nucleus coated with biocompatible material carrying functional groups determining specific biological activity of particular quantum dots. Generally, they are used in biological studies for specific staining of cells and tissues (streptavidin conjugates, antibody conjugates), Western blot analyses and visualization in vivo. For example, antibody-conjugates quantum dots recognize DNA sequences with typical cancer mutation. It is also used for analysis of drug distribution in vertebrates. The reduced toxicity of semiconductor quantum dots was achieved by using carbon nanoparticles (carbon dots); their surface exhibits photoluminescent properties.4
Quantum dot (QD) technology is also used to gather information about how the CNS environment becomes inhospitable to neuronal regeneration following injury or degenerative events by studying the process of reactive gliosis. Glial cells, housekeeping cells for neurons have their own communication mechanisms that can be triggered to become reactive following injury. QDs are being used to build data capture devices that are easy to use by neuroscientists, and a new protocol has been developed for tracking glial activity. Other research is looking at how QDs might spur the growth of neurons by adding bioactive molecules to the QDs as a means to provide a medium that will encourage growth in a directed way.4
 
Colloidal Gold (Au) Particles
They are inert and very useful as labels for TEM, but detectable in cells mostly by TEM and Raman spectroscopy. Its uses include bioimaging, heat induced killing of tumor cells and drug delivery. Gold nanoparticles can help X-ray's kill cancerous cells more effectively in mice. The technique works because gold, which strongly absorbs X-rays, selectively accumulates in tumors. This increases the amount of energy that is deposited in the tumor compared with nearby normal tissue. Because the gold is visible on CT and planar X-rays, it can be useful for early imaging and detection of tumors. Efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest their use as selective photothermal agents in molecular cancer cell targeting.5
 
Superstructures (Nanowires, Dendrimers, Nanocages)
Word dendrimers comes from the Greek Dendron meaning ‘tree.’ It includes creation on nanosensors based on new nanomaterials particularly dendrimers. Dendrimers are obtained by controlled molecular self-assembly of monomers. Selection of monomers determines properties (optical, magnetic or chemical) of the resultant polymer and high affinity to molecules of interest. For example, a new method for detection of cancer cells is based on the introduction of spherical nanosensors based on the 8dendrimers with special fluorescent layer into lymphocytes. Fluorescence intensity reflects changes induced by immune response of lymphoid cells. Early diagnosis of cancer is one of the most important directions of Nanodiagnostics.6
Product
Application
Vivagel
Vaginal gel for preventing HIV
Stratus CS
Cardiac marker
Superfect
Gene transfection
Alert Ticket
Anthrax detection
 
Advantages of Phospholipid Transport System
Phospholipids transport system is nontoxic, biodegradable and do not cause allergic reactions. So this transport system is also known as colloid inert transport systems. In past two decades, most significant research has been achieved in the development Phospholipid Transport System.
Bionanomaterials in use presently in different conditions (Table 1-1).
Table 1-1   Bionanomaterials
Orthopedics
Total hip and knee replacements, spinal implants, bone fixators and tendon and ligament prostheses
Cardiovascular system
Artificial heart valves, vascular grafts and stents, pacemakers, and implantable defibrillators
Plastic and reconstructive
Breast augmentation or reconstruction, maxillofacial
surgery
reconstruction, artificial larynx, penile implants, and injectable collagen for soft tissue augmentation
Neurosurgery
Cochlear implants and cerebrospinal fluid drainage systems (e.g. hydrocephalus shunts)
Ophthalmics
Contact and intraocular lenses
Drug-dispensing implants
Insulin pumps
General surgery
Sutures, staples, adhesives, and blood substitutes
 
Nanobiosensors in Diagnosis
The rapid and highly sensitive diagnostics represents an important step in therapy of any disease. The introduction of nanotechnologies into genomics and proteomics (e.g. optical biosensor, atomic force, nanowire and nanoporous based approaches) will significantly increase sensitivity and specificity of diagnostics and shorten time required for diagnostic procedure.2,6
In modern proteomics, the concentration barrier for detection and identification of protein molecules in biological material is about 10−12 molar 9concentration, whereas sensitivity of the methods of radioimmune analysis (RIA) and ELISA is within the range 10−12 to 10−15 molar concentration. The successful development of proteomics is determined by the development and introduction of methods characterized by capacities for detection and identification of proteins and their complexes in a wide concentration range (from 10−3 to 10−20 molar concentration).
Most widely used commercially available biosensors are the 4-channel SPR biosensors BIAcore (BIAcore, Sweden) for detection of markers of hepatitis B and C. Using the optical biosensor and chips with antibodies (anti-HBsAg) immobilized on the chip surface, it is possible to detect the Australia antigen, HBsAg in blood or serum of patients. Sensitivity is similar to originally employed methods such as ELISA. These methods have evident advantages that it is rapid (5–8 min) and biochip. It can be reused 100–150 times; thus reduces the cost significantly.
 
NANOPARTICLES FOR MOLECULAR IMAGING
The advent of nanotechnology led to magnetic resonance imaging (MRI) molecular agents that enable detection of sparse biomarkers with a high-resolution imaging. A wide variety of nanoparticulate MRI contrast agents are available, most of which are superparamagnetic iron oxide-based constructs. Perfluorocarbon (PFC) nanoparticles platform is not only effective as a T1-weighted agent, but also supports 19F magnetic resonance spectroscopy and imaging. Ultrasmall superparamagnetic iron oxide (USPIO) is a cell-specific contrast agent for MRI. An open-label phase II study has tested the potential of USPIO enhanced MRI for macrophage imaging in human cerebral ischemic lesions. USPIO-induced signal alterations differed throughout from signatures of conventional gadolinium-enhanced MRI, thus being independent from breakdown of the blood-brain barrier (BBB). Macrophages, as the prevailing inflammatory cell population in stroke, contribute to brain damage. USPIO-enhanced MRI may provide an in vivo surrogate marker of cellular inflammation in stroke and other central nervous system (CNS) pathologies.7
 
NANOPARTICLES IN RADIOLOGY
X-ray's radiation is widely used in medical diagnosis. Now, X-ray's radiation can be generated using carbon nanotube (CNT)-based field emission cathode. The CNT-based cathode X-ray's technology can potentially lead to portable and miniature X-ray's sources for medical applications. An X-ray's device based on CNTs emits a scanning X-ray's beam composed of multiple smaller beams, while also remaining stationary. As a result, the device can create images of objects from numerous angles and without mechanical motion, which is a distinct advantage for any 10machine because it increases imaging speed, reduce the size of the device, and requires less maintenance. This technology can lead to smaller and faster X-ray's imaging systems for tomographic medical imaging such as computed tomography (CT) scanners. Other advantages of scanners are cheap, uses less electricity, and produce higher-resolution images.8,9
 
NANOENDOSCOPES
Video capsule endoscopy is a major innovation that provides high-resolution imaging of the small intestine. Capsule endoscopy has demonstrated its viability as a first-line investigation in patients with obscure gastrointestinal bleeding after a negative esophagogastroduodenoscopy and colonoscopy, and it has a positive impact on the outcome. Video capsule endoscopy is also useful in the evaluation of inflammatory and neoplastic disorders of the small bowel. The positioning and movement on a nanoscale will greatly improve the accuracy of this method.10
Endoscopic microcapsules or “gutbots,” which are in development, are based on nanotechnology including nanosensors and sticking devices. These can be ingested and precisely positioned. A control system allows the capsule to attach to the walls of the digestive tract and move within its lumen. Precisely positioned microcapsules would enable physicians to view any part of the inside lining of the digestive tract in detail and result in more efficient, accurate, and less invasive diagnosis. In addition, these capsules could be modified to include treatment mechanisms as well, such as the release of a drug or chemical near an abnormal area. Similar nanorobots are under development for other parts of the body.18
 
NANOPARTICLES AS DRUGS
In recent years nanoparticles and nanomaterials become widely used for diagnostics and medical treatment. Nanoparticles as drugs have several important advantages such as increased solubility and high rate of solubilization, increased bioavailability, rapid therapeutic effect and decreased risks of side effects.2,3,1113
  1. Nanoprobes (USA) of gold nanoparticles for diagnosis of cancer: conjugates of antibodies against EGFR (epidermal growth factor receptor), which is not expressed by normal cells with gold particles bound to tumor cells could be easily detected during microscopy of biopsy material.
  2. Silica-based nanoparticles and nanocapsules for brachytherapy of inoperable hepatic cancer. Radioactive 32P incorporated into such capsules kills tumor cells.
  3. Phosphogliv(contains soybean phosphatidylcholine and glycyrrhizin) in an injection form represents particles up to 50 nm in diameter.11
    Phosphogliv caused inhibition of replication activity of hepatitis B and C viruses and positive effect on immune interferon status. Phosphogliv has low toxicity, causes no allergic reactions and is stable during storage.
 
NANOPARTICLES AS TRANSPORT SYSTEM OF DRUG
The construction of radical preparation design of new drugs involves a system, which deliver a medicinal substance directly to target organ or even target cells. Advantages include increased solubility of hydrophobic drugs, better penetration inside cells and improved pharmacokinetics (many drugs acquire ability to penetrate through membrane and blood brain barrier). 10–15 certified nanosystems are being used as drug carriers in the world. These are mainly Antitumor preparation equipped with Phospholipid transport system (Liposomes), e.g. Daunomycin, Doxorubicin, Vincristine, Annamycin, Tretinoin Depot-dur (Morphine Liposomes), Ambisome (Amp. B liposomes).
Other types of transport system are based on nanocapsule coated by dielectric material (Silicone and Gold). In this system, release of encapsulated drug occur after nanocapsule melting induced by radiation. This technology is being applied for treatment of diabetes mellitus. Dose dependent release of insulin occurred after heating of skin surface, where nanocapsules have been administered.
 
NANOTECHNOLOGY-BASED HUMAN NEPHRON FILTER (HNF) FOR RENAL FAILURE14,15
Patients with renal failure from end stage renal disease require treatment through dialysis or renal transplantation. Although various forms of renal replacement therapy are available for last four decades, mortality and morbidity is high and patients often have a poor quality of life. HNF development could eventually enable a continuously functioning, portable or implantable artificial kidney. HNF is the first in developing a renal replacement therapy to potentially eliminate the need for dialysis or kidney transplantation in end stage renal disease patients. HNF utilizes a unique membrane system created through applied nanotechnology and eliminate dialysate. It represents a breakthrough in renal replacement therapy. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.
Nanomaterials offer excellent reabsorption characteristics as it has very large surface area >1000 m2/gram, tunable chemistry for chemical selectivity and tunable porosity for molecular size selectivity.
 
NANOLASERS IN SURGERY
Laser surgery was used both for ablation and repair of tissues. Mechanical devices such as microneedles are too large for the cellular scale, whereas 12biological and chemical tools can only act on the cell as a whole rather than on any one specific mitochondrion or other structure. Furthermore manipulation of cellular structures at micrometer and nanoscale is an open field of nanoscale laser surgery. Femtosecond laser pulses can selectively cut a single strand in a single cell in the worm and selectively knock out the sense of smell. One can target specific organelle inside a cell without disrupting the rest of the cell. It is possible to carve channels slightly less than 1 micron wide, well within a cell's diameter of 10–20 microns. This technology might be scaled up to do surgery without scarring or perhaps to deliver drugs through skin. Near infra red femtosecond laser pulses have been applied in combination of microsurgery and nanosurgery on fluorescently labeled structures within cells. Femtolaser is already in use in corneal surgery. This has been also used for axotomy in round worm. It acts like a pair of tiny nanoscissors that is able to cut nanonsized structures like nerve axons. The pulse has a very short length, making photons in laser concentrate in one area, delivering much power to a tiny, specific volume without damaging surrounding tissues. Once cut, the axons vaporize and no other tissue is harmed. The application of this precise surgical technique should enable the study of nerve regeneration in vivo.1,16
 
NANOROBOTICS
Robotics is already developing for applications in life sciences and medicine. Robots can be programmed to perform routine surgical procedures. Nanobiotechnology introduces another dimension in robotics, leading to the development of nanorobots. Instead of performing procedures from outside the body, it can be miniaturized for introduction into the body through the vascular system or at the end of catheters into various vessels and other cavities in human body. Various functions such as searching for pathology, diagnosis and removal or correction of the lesion by nano manipulation can be performed and coordinated by an on-board computer. Nanorobots are cable of performing precise and refined intracellular surgery, which is beyond the capability of manipulations by human hand.17
 
NANOBIOTECHNOLOGY IN GENE THERAPY
The success of gene therapy for clinical applications in part would depend on the efficiency of expression of vector as determined by the level as well duration of gene expression. Vectors are usually viral but several nonviral techniques are being used as well. Genes and DNA are being introduced without the use of vectors and various techniques are now being used to modify the function of genes in vivo without gene transfer. Nanoparticles and other nanostructures can be used for gene delivery. Although various cationic polymers and lipid based systems are being investigated, most of 13these systems exhibit higher level but transient gene expression. Therefore, gene expression system that can modulate the level as well as duration of gene expression in target tissue is desirable. Polymer based sustained release formulations such as nanoparticles have the potential of developing into such a system.2
Nanotechnology may be used in development of tissue engineering as indicated by some studies in life sciences. Microfluidic devices enable the study of methods for patterning cells, topographical control over cells and tissues and bioreactors. Two major contributions includethe following;19
  1. The growth of complex tissue, where microfluidic structures ensure a steady blood supply, thereby circumventing the well known problem of providing larger tissue structures with a continuous flow of oxygen as well nutrition and removal of waste products.
  2. Microfluidics combined with nanotechnologylies in development of in vitro physiological systems for studying fundamental biological phenomenon.
 
NANOTECHNOLOGY IN THERAPY OF CANCER
The major innovations are in diagnostics and drug delivery system for cancer. A nanobody with subnanomolar affinity for human tumor associated CEA has been identified. This nanobody was conjugated to enterobacter cloacae beta-lactamase and its site selective anticancer prodrug activation capacity was evaluated. In vitro this complex effectively activated the release of phenylenediamine mustard from cephalosporin mustard at the surface of CEA-expressing LS174T cancer cells. In vivo, the conjugate had an excellent biodistribution profile and induced regressions and cures of established tumor xenografts. Thus nanobodies appears to be a promising vehicle for new generation cancer therapeutics.1,2,20,21
Nanoshells may be combined with targeting proteins and used to ablate target cells. This procedure can result in destruction of solid tumors or possibly metastases not otherwise detectable by oncologists. In addition, nanoshells can be utilized to reduce angiogenesis present in cancer. The advantages of nanoshell based tumor cell ablation include the following.
  1. Specific targeting of cells and tissues to avoid damage to surrounding tissue.
  2. Safer side effects profile than targeted chemotherapeutic agents or photodynamic therapy.
  3. Seamless integration of cancer detection and therapy.
  4. Repeatability because of no tissue memory, biocompatibility and ability to treat metastases and inoperable tumors.
Nanotechnology can be used to devise a nanobomb that can literally blow up tumors. Nanobombs are selective, localized and minimally invasive. Nanoclusters (gold nanobombs) can be activated in cancer cells 14only by confining near infrared laser pulse energy within critical mass of nanopartilces in the nanoclusters.
Carbon nanotubes hold great promise as therapeutic agent for killing cancer cells particularly breast cancer cells. Its effects can be spread over a wide area to create structural damage to surrounding cancer cells. Once tumor cells are killed, macrophages can effectively clear the cell debris and the exploded nanotube along with it.
 
PEPPLES (PROBES ENCAPSULATED BY BIOLOGICALLY LOCALIZED EMBEDDING) FOR BRAIN TUMOR THERAPY
PEPPLE nanosensors consist of sensor molecules entrapped in a chemically inert matrix by a microemulsion polymerization process that produces spherical sensors in the size range 20–200 nm. These sensors are capable of real time inter and intracellular imaging of ions and molecules and are insensitive to interference from proteins. In human plasma, they demonstrate a robust oxygen-sensing capability, little affected by light scattering and autofluorescence. PEPPLE has been developed as a tool for diagnosis as well treatment of cancer.1,2
PEPPLEs have been designed to carry a variety of agents on their surface, each with unique function. This multi-fuctionality is the major potential advantage of using nanoparticles to treat cancer. One target molecule immobilized on the surface could guide PEPPLE to tumor cell, another help to visualize the target using MRI, while third agent could deliver a destructive dose of drug or toxin to cancer cells. All three functions can be combined in a tiny polymer sphere to make a potent weapon against cancer.
PEPPLEs are inert and harmless until light is switched on. Used in combination with MRI imaging, it kills cancer cells at will, while tracking the effectiveness of treatment with imaging. PEPPLEs are highly localized to cancer target and do very little damage to surrounding healthy tissue. PEPPLEs and other nanoparticle drugs could also avoid another serious problem occurring in traditional chemotherapy, i.e. development of drug resistance.1,2,22
 
NANOTECHNOLOGY IN OPHTHALMIC DISORDERS
Photodynamic therapy is being used for exudative macular degeneration. This modality of therapy can be refined using a supra-molecular nanomedical device, i.e. dendritic photosensitizer encapsulated by a polymeric micelle formulation. It prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. Since its highly selective accumulation in choroidal neovascularization, it results in effective occlusion of choroidal neovascularization with minimal unfavourable phototoxicity.2315
Dendrimer glucosamine 6-sulphate has been shown to block fibroblast growth factor-2 mediated endothelial cell proliferation and neoangiogenesis in human matrigel and placental angiogenesis assays. Synthetically engineered dendrimers can be tailored to have defined immuno-modulatory and antiangiogenic properties and they can be used synergistically to prevent scar tissue formation.23
 
NANOTECHNOLOGY IN CARDIOVASCULAR DISEASES
The recent advances in nanotechnology and nanoscience offer a wealh of new opportunities for diagnosis and therapy of cardiovascular diseases. Working group in USA discussed various aspects of nanotechnology and its applications to heart, lung and blood products and the cardiovascular complications of sleep apnea.1,24
  1. Cardiac monitoring in sleep apnea: Since sleep apnea is a cause of irregular heartbeat, hypertension, heart attack and stroke, it is important that patients should be diagnosed and treated before these highly deleterious sequelae occur. In patients of sleep apnea, in vivo sensors can constantly monitor blood concentrations of oxygen and cardiac function during sleep. In addition, cardiospecific antibodies tagged with nanoparticles may allow physician to visualize heart movement, while a patient experiences sleep apnea to determine both short and long term effects of apnea on cardiac function.
  2. Unstable plaques in arteries: The diagnosis and treatment of unstable plaque is an area in which nanotechnology may have an immediate impact. Targeted nanoparticles multi-functional macromolecules can deliver therapy to a specific site, localized drug release being achieved either passively or actively. It can also stabilize vulnerable plaque by removing material, e.g. oxidized low density lipoproteins. Devices may be able to attach to unstable plaques and warn patients and care givers of plaque rupture.
  3. Repair of cardiovascular system: Nanotechnology may facilitate repair and replacement of blood vessels, myocardium and myocardial valves. It may also be used to stimulate regenerative processes such as therapeutic angiogenesis for ischemic heart disease. Nanoscaffolds and microscaffolds are needed to guide tissue repair and replacement in blood vessels and organs. Nanofiber meshes may enable vascular grafts with superior mechanical properties to avoid patency problems common in synthetic grafts, particularly small diameter grafts. Cytokines, growth factors and angiogenic factors can be encapsulated in biodegradable microparticles or nanoparticles and embedded in tissue scaffolds and substrates to enhance tissue regeneration. Scaffolds mimicking cellular matrices should be able to stimulate the growth of new heart tissue and direct revascularization.16
  4. Percutaneous angioplasty: The restenosis after coronary intervention continues to be a serious problem in cardiology. The recent advances in nanoparticle technology have enabled the delivery of NK911, an antiproliferative drug, selectively to the balloon-injured artery for a longer time. NK911 is a core-shell nanoparticle of polyoxyethylene glycol-based block copolymer encapsulating doxorubicin. It accumulates in vascular lesions with increased permeability. Currently available stents implanted in arterial lumens have problems with imaging within the stent structure, where potential restenosis can occur. A thin-film nanomagnetic particle coating solution can enable non-invasive, MRI based imaging of these devices. Nitric oxide (NO)-eluting nanofibers are being developed for incorporation into drug-eluting stents for anti-throbogenic action. NO has vasodilating action as well, which may be beneficial in ischemic heart disease.
 
NANOTECHNOLOGY IN ORTHOPEDICS
In orthopedics implants, biomaterials (usually titanium and/or titanium alloys) often become encapsulated with undesirable soft, fibrous but not hard bony tissue. Although possessing intriguing electrical and mechanicalproperties for neural and orthopedic applications, carbon nanofibers/ nanotubes have not been widely considered for these applications previously. A carbon nanofibers reinforced polycarbonate urethane composite has been developed in an attempt to determine the possibility of using carbon nanofibers as orthopedic prosthetic devices. Mechanical characterization studies had shown that such composites have properties suitable for orthopedic applications. These materials enhance function of osteoblasts and decreased functions of cells that lead to fibrous-tissue encapsulation events for bone implants.
Single walled carbon nanotubes (SWNTs) have been used as scaffolds for growth of artificial bone materials. The strength, flexibility and light weight enable them to act as scaffolds to hold up regenerating bone. SWNTs can mimic the role of collagen as scaffolds for inducing the growth of hydroxyappetite crystals. On chemical treatment of nanotubes, it is possible to attract calcium ions and promote the crystallization process while improving the biocompatibility of nanotubes.1,3
 
NANOTECHNOLOGY IN DERMATOLOGICAL DISEASES
Long term topical steroid can induce skin atrophy by inhibition of fibroblasts. Therefore there is a need of drug carriers that may contribute reduction of this risk by epidermal targeting. Prednicarbate was incorporated into solid lipid nanoparticles of various compositions and was found to have localizing effects in epidermal layers.1,317
Topical nanocreams containing nanocrystalline silver have been demonstrated to have exceptional anti-microbial properties. It has been successfully used in wound healing and treatment of various inflammatory disorders of skin. It has also been found that its efficacy were equivalent to immunosuppressant tacrolimus ointment. Polyurethane membrane produced via electrospinning is useful as wound dressing due to its following properties:
  1. It soaks fluid from wound so that it does not build up under the covering.
  2. Does not cause wound dessication.
  3. Water loss by evaporation is also controlled.
  4. Excellent oxygen permeability and inhibits exogenous invasion of micro-organisms.
  5. Enhances rate of epithelization.
  6. Well-organized dermis.
 
SUMMARY AND CONCLUSION
The initial concept of nanomedicine has originated from fantastic ideas of creation and introduction to the human body of “tiny” nanorobots and related mechanisms, which would be responsible for cell repair at the molecular level. After 10–20 years, the development and improvement of nanotechnologies results in employment of first nanorobots in the consulting rooms of general practitioners; this would give medical doctors effective “weapons” to fight against any disease. Nanorobots might be analogues of blood cells (erythrocytes, phagocytes, respirocytes, etc.) tfus significantly exceeding effectiveness of functions of real blood cells. On the other hand, this will give new capacities for substitution of gene therapy for gene surgery. A nanorobot controlled by doctors will isolate a mutant gene from a single ill cell and introduce a normal gene into the same cell (and into right position). Possibility of cell penetration with the “laser scalpel” without impairments of the cell structure has recently been demonstrated. However, there are many technical problems, which should be solved on the way of creation of real medical nanorobots. Thus, introduction of nanotechnologies into biology and medicine will significantly extend their capacities in the nearest future.
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