Impact of Nanotechnology on Biomedical Sciences: Review of Current Concepts on Convergence of Nanotechnology With Biology

Impact of Nanotechnology on Biomedical Sciences: Review of Current

Concepts on Convergence of Nanotechnology With Biology

Herbert Ernest and Rahul Shetty

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Submitted: March 26th, 2005

Posted: May 18th 2005

Topics Covered
Abstract
Background
Recent Developments
Nano-DNA Technology
Nanobiotechnology in High-Throughput Single Nucleotide Polymorphism Analysis
Nanoparticles as Biomarkers
Nanotechnology in Measurements of Dissolved Oxygen
Application of Nanotechnology to P450 Enzymes
Application of Nanotechnology to Tissue Engineering
Growth of New Organs
Molecular Imaging
Summary
Acknowledgements
References
Contact Details

Abstract

Two of 21st century’s most promising technologies are biotechnology and nanotechnology.
This science of nanoscale structures deals with the creation, investigation and utilisation of
systems that are 1000 times smaller than the components currently used in the field of
microelectronics. Biotechnology deals with metabolic process with microoraganisms.
Convergence of these two technologies results in growth of nanobiotechnology. This
interdisciplinary combination can create many innovative tools.
The biomedical applications of nanotechnology are the direct products of such convergences.
However, the challenges facing scientists and engineers working in the field of nanotechnology
are quite enormous and extraordinarily complex in nature.
Utility of nanotechnology to biomedical sciences imply creation of materials and devices
designed to interact with the body at sub-cellular scales with a high degree of specificity. This
could be potentially translated into targeted cellular and tissue-specific clinical applications
aimed at maximal therapeutic effects with very limited adverse-effects.
Nanotechnology in biomedical sciences presents many revolutionary opportunities in the fight
against all kinds of cancer, cardiac and neurodegenerative disorders, infection and other
diseases.
This article presents an overview of some of the applications of nanotechnology in biomedical
sciences.

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 Herbert Ernest and Rahul Shetty

Background
Nanotechnology is a new area of science that involves working with materials and devices that
are at the nanoscale level. A nanometre is billionth of a meter. That is, about 1/80,000 of the
diameter of a human hair, or ten times the diameter of a hydrogen atom. It manipulates the
chemical and physical properties of a substance on molecular level. Nanotechnology alters the
way we think, it blurs the boundaries between physics, chemistry and biology, the elimination
of these boundaries will pose many challenges and new directions for the organisation of
education and research.
Richard Feynman’s speech called ‘There is plenty of room at the bottom’ in 1959 emphasised
this concept - If our small minds, for some convenience, divide this universe into parts,
physics, biology, geology, astronomy, psychology and so on – Remember that nature does not
know it [1].
Nanobiotechnology is the unification of biotechnology and nanotechnology. This hybrid
discipline can also mean making atomic-scale machines by imitating or incorporating biological
systems at the molecular level, or building tiny tools to study or change natural structure
properties atom by atom. Nanobiotechnology can have a combination of the classical micro-
technology with a molecular biological approach. Biotechnology uses the knowledge and
techniques of biology to manipulate molecular, genetic, and cellular processes to develop
products and services, and is used in diverse fields from medicine to agriculture. Convergence,
is an activity or trend that occurs based on common materials and capabilities-in this case the
discipline that enables convergence is nanotechnology. The potential opportunities offered by
this interface is truly outstanding; the overlap of biotech, nanotech and information technology
is bringing to fruition many important applications in life sciences.
This technology is expected to create innovations and play a vital role in various biomedical
applications (fig. 1), not only in drug delivery and gene therapy, but also in molecular imaging,
biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of
pathologies are the priority research areas where nanotechnology would play a prominent role
[2].

Figure1. Schematic illustration of nanotechnology revolutionising biomedical sciences.

The National Institutes of Health Bioengineering Consortium (BECON) held a symposium in
2000 entitled “Nanoscience and Technology: Shaping Biomedical Research″[3]. Eight areas of
nanoscience and nanotechnology were addressed at the conference and believed to be the
most pertinent to research in biomedicine. These areas included synthesis and use of

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 Impact of Nanotechnology on Biomedical Sciences: Review of Current Concepts on Convergence of Nanotechnology With Biology

nanostructures, applications of nanotechnology to therapy, biomimetic and biologic

nanostructures, electronic-biology interface, devices for early detection of disease, tools for the
study of single molecules, nanotechnology and tissue engineering.
The aim of BECON was to enhance communication between biomedical scientists and
engineers who bring different aspects of their skills and knowledge to bear on these problems
and to make the biomedical community more aware of the emerging developments in the field
of nanotechnology. The deliberations of the conference are now widely reinforced by day-to-
day experience, increasing ability to manipulate individual molecules at a nanoscale and to
combine biomolecules with other nanoscale structures. This ability provides the opportunity for
untold new therapeutic and diagnostic applications by enabling the building of novel structures
from the bottom up [4].
In the foreseeable future, the most important clinical application of nanotechnology will
probably be in pharmaceutical development. These applications take advantage of the unique
properties of nanoparticles as drugs or constituents of drugs or are designed for new strategies
to controlled release, drug targeting, and salvage of drugs with low bioavailability [5-7].
Nanoscale polymer capsules can be designed to break down and release drugs at controlled
rates, to allow differential release in certain environments, such as an acid medium, and to
promote uptake in tumours versus normal tissues [8]. A lot of research is now focused on
creating novel polymers and exploring specific drug-polymer combinations. Nanocapsules can
be synthesized directly from monomers or by means of nanodeposition of preformed polymers
[9]. Nanocapsules have also been formulated from albumin and liposomes. Implantable drug
delivery systems that are being developed will make use of nanopores to control drug release.
One of the key issues in bio-availability is cell transfection in DNA gene therapy. Current
methods have significant limitations, including the risk of inadvertent transmission of disease
by viral vectors. This has led researchers to explore polymer-DNA complexes and liposome-
DNA complexes for gene delivery [10]. It has also been shown that compacted DNA in the
form of nanoparticles can be used to transfect postmitotic cells [11].
Despite the risk and limitations, viral vectors are an efficient biomimetic approach to drug
targeting and delivery. The tat peptide from human immunodeficiency virus (HIV) and other
viral proteins are being attached to DNA, proteins, and other materials for uptake into cells.
These nano-assemblies mimic the action of the fusion proteins that make viral transfection
efficient [12, 13]. Nanotechnology has also enabled the development of biochips and has a role
in green manufacturing (e. g biocompatibility and biocomplexity areas). Other applications
include the design of sensors for astronauts, soldiers, biofluids (for handling DNA and other
molecules), in vitro fertilization of live stock, nanofiltration, bioprocessing ‘by design’ and
traceability of genetically modified food (Table 1).
Table 1. List of Nanotechnology applications to Biomedical sciences

Nano-Applications References
Bio-detection of pathogens 15
Detection of proteins 16
Probing of DNA structure 17
Tissue engineering 18, 19
Heat destruction of tumour (hyperthermia) 20
Phagokinetic studies 21
MRI Contrast enhancement 22
Separation and purification of biomolecules and cells 23
Fluorescent biological markers 24, 25
Drug and gene delivery 26, 27
Artificial cells and their assemblies 28
Design of proteins for efficient electron transport or with mechanical 29
features
Using dip pen technology 30, 31

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 Herbert Ernest and Rahul Shetty

Formation and growth of nanostructures in living biosystems (e.g by 32

alfalfa plants)
Biosensors 33
Nanobiomotors 34-36
Biomineralization 37
Nanorobotics 14, 38
Nanocomputers 39
Nanorods for vaccination applications 40
Exploratory areas for nanotechnology will include research into the condition and/or repair of
the brain and other areas for regaining cognition. It might also find application in designing
pharmaceuticals as a function of patient genotypes and in applying chemicals to stimulate
production as a function of plant genotypes. The synthesis of more effective and biodegradable
chemicals for agriculture and the production of implantable detectors could be aided by
nanotechnology with minimal quantities of blood. Employing this technology it should also be
possible to develop methods that use saliva instead of blood for the detection of illnesses or
that can perform complete blood testing within a short period of time. Broader issues include
economic molecular medicine, sustainable agriculture, conservation of biocomplexity, and
enabling emerging technologies.
Richard E. Smalley, winner of the 1996 Nobel Prize in Chemistry announced in his
congressional testimony to the U.S. government about the increasing awareness in the
scientific and technical community of our entry into a new golden age. Burgeoning interest in
the medical applications of nanotechnology has led to the emergence of a new discipline
known as nanomedicine [14]. On a wider scope, nanomedicine is the process of diagnosing,
treating, preventing disease and traumatic injury, of relieving pain, and of preserving and
enhancing human health, using molecular tools and molecular knowledge of the human body.
The purpose of this review is to throw more light on the recent advances and impact of
nanotechnology on biomedical sciences.

Recent Developments
Medical diagnosis with appropriate and effective delivery of pharmaceuticals are the medical
areas where nanosize particles have found practical applications. However, there are many
other interesting proposals for the use of nanomechanical tools in the fields of medical
research and clinical practice. Such nanotools are awaiting construction, and presently are
more like a fantasy. Nevertheless, they might be quite useful, and become a reality in the near
future [41].
Nanodevices in medical sciences could function to replace defective or improperly functioning
cells, such as the respirocyte proposed by Freitas [42]. This man-made red blood cell is
theoretically capable of providing oxygen more effectively than an erythrocyte. It could replace
defective natural red cells in blood circulation. Primary applications of respirocytes may involve
transfusable blood substitution, partial treatment of anaemia, prenatal/neonatal problems, and
lung disorders.
It has been reported that nanomachines could administer drugs within a patient’s body. Such
nanoconstructions could deliver drugs to peculiar sites making treatment more accurate and
precise [43]. Similar machines with specific ‘weapons’ could be used to remove obstacles in
the circulatory system or in the identification and killing of tumour cells.
The other vital application of nanotechnology in relation to medical research and diagnostics
are nanorobots. Nanorobots, operating in the human body, could monitor levels of different
compounds and record the information in the internal memory. They could be rapidly used in
the examination of a given tissue, surveying its biochemical, biomechanical, and histometrical
features in greater detail. Just as biotechnology extends the range and efficacy of treatment
options available from nanomaterials, the advent of molecular nanotechnology will again
expand enormously the effectiveness, comfort and speed of future medical treatments while at
the same time significantly reducing their risk, cost, and invasiveness.
Biotechnology permits tailor-made production and biopharmaceuticals and biotechnological

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 Impact of Nanotechnology on Biomedical Sciences: Review of Current Concepts on Convergence of Nanotechnology With Biology

drugs, many of which require special formulation technologies to overcome drug-associated

problems. Such major challenges to solve include the following: poor solubility, limited
chemical stability in vitro and in vivo after administration (i.e. short half-life), poor
bioavailability and potentially strong side-effects requiring drug enrichment at the site of action
(targeting) [44]. Nanoparticulate carriers have been developed as one solution to overcome
such delivery problems, i.e. drug nanocrystals, solid lipid nanoparticles (SLN), nanostructured
lipid carriers (NLC) and lipid-drug conjugate (LDC) nanoparticles [44]. The carriers as reported
by Muller and colleagues are suitable to solve delivery problems with biotech drugs of different
solubility. Targeting with these carriers can be realised by a very simple approach, the
differential protein adsorption (PathFinder® technology). This technology proved to be efficient
enough to accumulate sufficiently high amounts of drugs in the brain to reach therapeutic
levels and also fulfill the major requirement to be pursued by a pharmaceutical company.
Quantum Dot with nanodots of a specific colour are believed to be flexible and could offer a
cheap and easy way to screen a blood sample for the presence of a number of different viruses
at the same time. It could also give physicians a fast diagnosis tool to detect, say, the
presence of a particular set of proteins that strongly indicates the onset of myocardial
infarction. On the research front, the ability to simultaneously tag multiple biomolecules both
on and inside cells could allow scientists to watch the complex cellular changes and events
associated with disease, providing valuable clues for the development of future
pharmaceuticals and therapeutics (Quantum Dot Corporation) [45].
The National Heart, Lung, and Blood Institute (NHLBI) plans to foster the application of
nanotechnology to HLBS (Heart, Lung, Blood and Sleep) research and disorders. A request for
information (RFI) was developed, with advice from scientists and physicians with interests in
nanotechnology, to canvas the broader scientific community on approaches to developing and
applying nanotechnology to HLBS disorders. A working Group comprising scientists, engineers,
and physicians with expertise across nanotechnology, nanoscience, and HLBS medicine met on
February 28th, 2003, using the RFI responses as the starting point for discussions. The Working
Group was entrusted with assessing the field of nanotechnology and suggesting ways for
research. The Working Group cautioned against overly rigid or restrictive definition of
nanotechnology, emphasizing the continuum of scale from the nanoscale to the microscale.
The Group also identified areas of opportunity and challenges to further development
associated with the application of nanoscience and nanotechnology to improved diagnosis,
treatment, and prevention of HLBS disorders. It as well developed prioritized recommendations
to facilitate the application of nanotechnology to biological questions and improved patient care
[46].
The RESIST Group at the Welsh School of Pharmacy at Cardiff University and others have
looked at how molecularly imprinted polymers could be medically useful in clinical applications
such as controlled drug release, drug monitoring devices, and biological and antibody receptor
mimics. Histamine and ephedrine molecularly imprinted polymers (MIPs) were studied as
potential biological receptor mimics whilst a propanolol MIP was investigated for its use as a
rate attenuating selective excipient in a transdermal controlled device [47].
The first artificial voltage-gated molecular nanosieve was fabricated by Charles R. Martin and
colleagues [48] at Colorado State University in 1995. Martin’s membrane contains an array of
cylindrical gold nanotubules with inside diameters as small as 1.6nm. When the tubules are
positively charged, positive ions are excluded and only negative ions are transported through
the membrane. When the membrane receives a negative voltage, only positive ions can pass.
Similar nanodevices may combine voltage gating with pore size, shape, and charge constraints
to achieve precise control of ion transport with significant molecular specificity. An exquisitely
sensitive ion channel switch biosensor was built by an Australian research group [49].
The year 2003 could be termed a very special year for biomedical research because we
celebrated the completion of the sequencing of the entire human genome which coincided with
the 50th anniversary of the discovery of the DNA double helix structure by Watson and Crick.
In biomedical imaging, we also witnessed the awarding of the Nobel Prize in Medicine and
Physiology to two pioneers in Magnetic Resonance Imaging, Professor Paul Lauterbur and Sir

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 Herbert Ernest and Rahul Shetty

Peter Mansfield. These landmark events helped to highlight the impact of the rapid
development in many diverse disciplines to biomedical research. The leverage and tremendous
advances in electronics and information technology has been brought about by biomedical
imaging research [50]. The opportunities and challenges in future biomedical research lie in
the incorporation of knowledge gained from molecular biology with chemistry, physics,
engineering, information technology, and nanotechnology to understand the ambiguity and
complexity of life and come up with new diagnostic and therapeutic methods.
Calcium phosphate nanoparticles present a unique class of non-viral vectors, which can serve
as efficient and alternative DNA carriers for targeted delivery of genes. The design and
synthesis of ultra-low size, highly monodispersed DNA doped calcium phosphate nanoparticles
of size around 80nm in diameter has been reported [51]. The DNA encapsulated inside the
nanoparticle is protected from the external DNase environment and could be used safely to
transfer the encapsulated DNA under in vitro and in vivo conditions.
The application of a combination of nanomedicine with biophotonics for optically tracking the
cellular pathways of gene delivery and the resulting transfection by using nanoparticles as a
non-viral vector has been demonstrated recently [52]. Gene delivery is an area of considerable
current interest; genetic materials (DNA, RNA, and oligonucleotides) have been used as
molecular medicine and are delivered to specific cell types to either inhibit some undesirable
gene expression or express therapeutic proteins.

Nano-DNA Technology
The discovery of the polymerase chain reaction (PCR) [53, 54] paved the way to a new era of
biological research. The impact can be felt not only in the field of molecular biology, but also in
other allied fields of science. Novel classes of semi-synthetic DNA-protein conjugates, self-
assembled oligomeric networks consisting of streptavidin and double-stranded DNA, which can
be converted into well-defined supramolecular nanocircles have been developed [55, 56].
The DNA-streptavidin conjugates are applicable as modular building blocks for the production
of new immunological reagents for the ultrasensitive trace analysis of proteins and other
antigens by means of immuno-PCR methodology [57-59]. Immuno-PCR is a combination of the
specificity of an antibody-based immuno-assay with the exponential power of the amplification
of PCR, hence resulting in a 1000-fold degree of sensitivity as compared with standard ELISA
(Enzyme-linked immunosorbent assay) methods.
Self-assembled DNA-streptavidin conjugates have also been applied in the field of
nanotechnology. For example, the conjugates are used as model systems for ion-switchable
nanoparticle networks, as nanometre-scale ‘soft material’ calibration standards for scanning
probe microscopy [60, 61], or as programmed building blocks for the rational construction of
complex biomolecular architecture, which may be used as templates for the growth of
nanometre-scale inorganic devices [62, 63]. Covalent conjugates of single-stranded DNA and
streptavidin are used as biomolecular adapters for the immobilization of biotinylated
macromolecules at solid substrates through nucleic acid hybridization. This ‘DNA-directed
immobilization’ allows for reversible and site-selective functionalization of solid substrates with
metal and semiconductor nanoparticles or, vice versa, for the DNA directed functionalization of
gold nanoparticles with proteins, such as immunoglobulins and enzymes. The fabrication of
functional biometallic nanostructures from gold nanoparticles and antibodies are applied as
diagnostic tools in bioanalytics [64].

Nanobiotechnology in High-Throughput Single Nucleotide Polymorphism Analysis

Following the publication of a map of variation in the human genome sequence containing over
two million single nucleotide polymorphisms (SNPs) (The International SNP Map Working
Group, 2001), the next challenge is the development of the technologies to use this
information in a cost-effective manner. Genotyping methods have to be improved in order to
increase throughput by at least two orders of magnitude to enable pharmaceutical,
biotechnological and academic research to uncover associations between genetic variants and
diseases, with consequent potential for the development of novel diagnostics and therapies.

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New approaches to DNA extraction and amplification have curtailed the times required for
these processes to seconds. Microfluidic devices enable polymorphism detection through very
rapid fragment separation using capillary electrophoresis and high-performance liquid
chromatography, together with mixing and transport of reagents and biomolecules in
integrated systems [65]. The basic objectives in the development of a DNA extraction and
purification system that will be compatible with high-throughput SNP genotyping requirements
are:
• Release of the DNA from the cells into solution without either enzymatic (i.e.
endonucleases) or mechanical (shearing) breakdown of the DNA;
• Removal of cellular debris (e.g. proteins) that may hamper DNA amplification or
hybridization assays;
• High-throughput and economical DNA sample preparation with simplified protocols that
reduce the number of procedures involved;
• Avoidance of hazardous chemical requirements as much as possible to minimize handling
and disposal costs;
• Consistency of both quality and quantity of DNA yield among samples so that quantification
is unnecessary, and subsequent amplification and/or hybridization can be to a high degree
of reproducibility;
• A highly efficient process, to ensure enough supply for the enormous number of assays
anticipated; and
• An interface that will enable direct loading of conventionally sampled biopsies on to the
system [65].
The potential for nanotechnology to contribute to rapid high-throughput SNP analysis is most
evident with smart biochip platforms. The development of an electronically addressable
microarray platform as described by Heller L. et al 2000 [66] has given rise to Nanogen Inc.
(San Diego, California, USA). The challenge of providing one or more technology platforms
capable of SNP screening throughput of the order of 107 genotypes per day will need to be
achieved, to allow significant associations between genes and diseases to be established.
Additionally, the technology platform(s) will also need to deliver economies of scale, such that
the cost per genotype will be less than 0.01$ for the magnitude of screening necessary to be
feasible. From the rapidly developing field of nanotechnology, novel tools and processes have
been introduced with the potential to provide the capabilities required [67-69].
Differences of SNPs occurring in close proximity to each other on the genome is normally
correlated due to linkage during the process of replication, and the extent of this correlation is
termed linkage disequilibrium. Where a significant association occurs between the genetic
variation observed at specific SNPs and the presence of a disease, susceptible genes can be
identified. The statistical estimations needed to eliminate false-positive results were reviewed
by McCarthy and Hilfiker (2000) [70]. They suggest a linear increase in sample size is
necessary for every order of magnitude increase in the number of markers tested. Hence,
positive identification of a susceptible gene from a screening programme including 1 Million
SNPs would require a minimum sample size of 1000 (i.e. a minimum of 109 SNPs have to be
screened).

Nanoparticles as Biomarkers
Nanoparticles can be used for both quantitative and qualitative in vitro detection of tumour
cells. They enhance the detection process by concentrating and protecting a marker from
degradation, in order to render the analysis more sensitive. For instance, streptavidin-coated
fluorescent polystyrene nanospheres Fluospheres® (green fluorescence) and
TransFluospheres® (red fluorescence) were applied in single colour flow cytometry to detect
the epidermal growth factor receptor (EGFR) on A431 cells (human epidermoid carcinoma
cells) [71]. The results have shown that the fluorescent nanospheres provided a sensitivity of
25 times more than that of the conjugate streptavidin-fluorescein.
New tools can now be developed, designed at the intersection of proteomics and
nanotechnology, whereby nanoharvesting agents can be instilled into the circulation (e.g.
derivatized gold particles) or into the blood collection devices to act as ″molecular mops″ that

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 Herbert Ernest and Rahul Shetty

soak up and amplify the bound and complexed biomarkers that exist [72-74]. These
nanoparticles, with their bound diagnostic cargo, can be directly queried via mass
spectrometry to reveal the low molecular weight and enriched biomarker signatures.
Ultimately, utility of any approach for detecting disease is assessed on its clinical impact to
patient outcome and disease-free survival [75]. What is urgently required in the study of
diseases in general, is the development of biomarkers that can detect curable diseases earlier,
and not detecting advanced disease better.
Contrast agents have been loaded onto nanoparticles for tumour diagnosis purposes. The
physico-chemical features (particle size, surface charge, surface coating, stability) of the
nanoparticles allow the redirection and the concentration of the marker at the specific site of
interest. Labelled colloidal particles could be used as radiodiagnostic agents. On the other
hand, some non-labelled colloidal systems are already in use and some are still being tested as
contrast agents in related diagnosis procedures such as computed tomography and NMR
imaging.
To date, a study of radionucleide use in diagnostic imaging with nanoparticles for cancer
detection is yet to be published. However, as conventional colloidal particles can be cells of
organs like the liver, the spleen, the lungs and the bone marrow and as long-circulating
nanoparticles can have a compartmental localization in the blood circulation or the lymphatic
system- all these organs being potential sites for tumour development, these colloidal systems
could potentially improve tumour diagnosis.
In the future, nanoparticles that are engineered with specific binding affinities can be
resuspended into the collected body fluids, or perhaps even injected directly into the
circulation. The nanoparticles, together with the bound molecules, could be directly captured
on engineered filters and directly questioned by ultra high-resolution mass spectrometry (e. g.
Fourier Transform Ion Cyclotron Resonance).

Nanotechnology in Measurements of Dissolved Oxygen

Oxygen is one of the major metabolites in aerobic systems, and the measurement of dissolved
oxygen is of vital importance in medical, industrial, and environmental applications. Recent
interest in the methods for measuring dissolved oxygen concentration has been focused mainly
on optical sensors, due to their advantages over conventional amperometric electrodes in that
they are faster, do not consume oxygen, and are not easily poisoned [76, 77].
Optical PEBBLE (probes encapsulated by biologically localized embedding) nanosensors have
been developed for dissolved oxygen using organically modified silicate (ormosil) nanoparticles
as a matrix. The ormosil nanoparticles are prepared through a sol-gel-based process, which
includes the formation of core particles with phenyltrimethoxysilane as a precursor followed by
the formation of a coating layer with methyltrimethoxysilane as a precursor [78]. The highly
permeable structure and the hydrophobic nature of the ormosil nanoparticles, as well as their
small size, result in an excellent overall quenching response to dissolved oxygen and a linear
response over the whole range, from 0 -100% oxygen-saturated water. This PEBBLE sensor
has a higher sensitivity and a broader linearity as well as longer excitation and emission
wavelengths, resulting in reduced background noise for cellular measurement. The PEBBLE
sensors are excellent in terms of their reversibility and stability to leaching and long-term
storage. A real-time monitoring of changes in the dissolved oxygen due to cell respiration in a
closed chamber was made by gene gun delivered PEBBLE. This sensor is now being applied for
simultaneous intracellular measurements of oxygen and glucose [78].

Application of Nanotechnology to P450 Enzymes

Cytochromes P450 are highly relevant to the bio-analytical area [79]. They form a large family
of enzymes present in all tissues essential to the metabolism of most drugs in use today,
playing a vital role in the drug development and discovery process. They act as catalysts for
the insertion of one of the two atoms of an oxygen molecule into a variety of substrates (R)
with quite broad regioselectivity, leading to concomitant reduction of the other oxygen atom to
water as shown in the equation below [29].

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 Impact of Nanotechnology on Biomedical Sciences: Review of Current Concepts on Convergence of Nanotechnology With Biology

RH + O2 + 2e − + 2H + → ROH + H2O
Several methods have been reported in the literature for the screening of substrate turnover
by P450s in a high throughput format [80-83]. However, they all fall short of being limited to
testing the activity of P450 enzymes through the detection of the conversion of a specific
marker substrate, but Tsotsou et al 2002 [84] have been able to develop a method called the
alkali method, which can detect the turnover of any NAD(P)H or NAD(P)+ dependent enzyme.
The progress on these research fronts and their combinations provide a powerful platform for
future applications of these enzymes, with particular reference to protein array technology.

Application of Nanotechnology to Tissue Engineering

Tissue engineering is based on the creation of new tissues in vitro followed by surgical
placement in the body or the stimulation of normal repair in situ using bioartificial constructs
or implants of living cells introduced in or near the area of damage. Though it is mainly
concerned with using human material, either from the patient themselves (autologous) or from
other human sources (allogeneic), material from other mammalian sources have also been
applied in humans (xenogeneic).
The involvement of microelectronics or nanotechnology in creating a truly bioartificial tissue or
organ that can take the place of one that is terminally diseased, such as an eye, ear, heart, or
joint has been envisaged. Implantable prosthetic devices and nanoscaffolds for use in the
growing of artificial organs are goals of nanotechnology researchers. Nanoengineering of
hydroxyapatite for bone replacement is reasonably advanced [85, 86].
In the future, we could imagine a world where medical nanodevices are routinely implanted or
even injected into the bloodstream to monitor wellness and to automatically participate in the
repair of systems that deviate from established norms. These nanobots could be personalized
by tailoring them to patient genotype and phenotype to optimize intervention at the earliest
stage in the course of disease expression [4].

Growth of New Organs

Nanoscale building of cells can be accomplished by their programmed replication. The signals
are transmitted back and forth with the instruction for the desired size and shape form the
construction site. When complete instructions are finished, the organs can be grown according
to the prerequisite specifications.
These organs could have the necessary DNA encoded to be compatible with the required
human body immunological status. This can enhance integration of artificial structures with
living tissues, presenting a more appropriate interface to biological systems. With the
advantage in absence of immune reaction unlike today’s donor organ transplantation. In the
years to come this can accomplish a Quantum leap in the management of organ failure
disorders.

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 Herbert Ernest and Rahul Shetty

Figure 2. Graphical representation of the nanoscale construction and growth of new organs.

Molecular Imaging
New imaging approaches using genetically encoded fluorescent and bioluminescent reporters
(i.e., illuminated or glowing identification tags) are offering revealing insights to the living body
as never observed before. Information provided by these reporters can be used to enhance our
understanding of human biology and the development of therapeutic approaches for many
diseases, including cancer, infection, neurodegenerative and cardiovascular disease.
In addition to progresses so far made with molecular agents, industry leaders are also
showcasing rapidly evolving imaging technologies that allow scientists to view organisms at the
molecular level (Table 2).
Table 2. Latest products in Molecular Imaging and associated producing Companies

Product Name Company(ies)

SPECT/CT hybrid imaging systems Philips Medical Systems/Siemens
Medical Solutions
GFAP-luc (glial fibrillary acid protein) Xenon
Ultrasound bubbles Schering AG
NeuroSpec™ (radiodiagnostic agent) Tyco Healthcare/Mallinckrodt Inc.
eXplore Locus Ultra (Volumetric CT system) GE Medical system
Definity® or Sonolysis™ (nanosurgery) ImaRx
• SPECT/CT hybrid systems capture both functional information on molecular and cellular
processes (growth and activity) and anatomical detail (size and shape) of a targeted
molecular structure more quickly, efficiently and clearly than standard imaging devices. The
images obtained from these systems can assist with the rapid identification of tumours,
analysis of appropriate treatment, delivery of targeted therapy to precisely destroy target
cells, and follow up to assess treatment effectiveness.
• Xenon presented its newer light producing transgenic animal models (GFAP-luc) during the
Society for Molecular Imaging’s 3rd Annual Meeting. This model may prove to be an
important model for tracking damage and repair in chronic neurological conditions such as
post-ischemic stroke or Parkinson’s disease.
• An ultrasound contrast agent is made of tiny “microbubbles″ that scatter light and allow
the clinician to see which part of the heart muscle is poorly functioning. The sensitivity and
flexibility of ultrasound makes it the most sensitive method of imaging microbubbles
because it deliberately disrupts the pattern and produces a very strong and highly
characteristic transient effect. For example,

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 Impact of Nanotechnology on Biomedical Sciences: Review of Current Concepts on Convergence of Nanotechnology With Biology

• Definity® otherwise known as Sonolysis™ are gas-filled microbubbles for novel therapeutic
applications. For dissolving vascular thrombosis, microbubbles are administered
intravenously to a patient or injected locally into a specific vascular structure such as a
vascular graft. Ultrasound is applied externally (or can be applied internally via catheter)
over the area of the blood clot to provide localized, targeted action. As the microbubbles
perfuse the clot, they act as micromechanical devices where ultrasound pulses the bubbles
and blows up the bubbles in the ultrasound field, leading to blood clot dissolution. Sonolysis
nanosurgery is locally targeted nanoinvasive therapy for treatment of vascular thrombosis.
Compared with alternative therapies for treating thrombosis, sonolysis affords the potential
merits of being less invasive than mechanical thrombectomy and faster than conventional
drug therapy with less risk of bleeding.
• NeutroSpec™ is a radiodiagnostic agent which labels white blood cells and myeloid
precursors without the need for removal and re-injection of blood into patients. This new
product is for patients with equivocal signs of appendicitis who are five-years-old and up.
NeutroSpec also facilitates the visualization of images generated via gamma camera
allowing physicians to quickly and easily locate the sites of infection thereby eliminating
time delays and/or risks normally affiliated with alternative white blood cell labelling
processes.
• eXplore Locus Ultra is a first-class volumetric CT system capable of quantitating
physiological measurements and elaborate anatomy of tissues, tumours and organ
perfusion. The Locus Ultra also performs image acquisition at the rate of a sub-second,
enabling dynamic imaging.

Summary
The multidisciplinary field of nanotechnology’s application for discovering new molecules and
manipulating those available naturally could be dazzling in its potential to improve health care.
The spin-offs of nanobiotechnology could be utilised across all the countries of the world.
In the future, we could imagine a world where medical nanodevices are routinely implanted or
even injected into the bloodstream to monitor health and to automatically participate in the
repair of systems that deviate from the normal pattern. The continued advancement in the
field of biomedical nanotechnology is the establishment and collaboration of research groups in
complementary fields. Such collaborations have to be maintained not only on specialty field
level, but internationally as well. The successful development and implementation of
international collaborations fosters a global perspective on research and brings together the
benefits to mankind in general. However, nanotechnology in medicine faces enormous
technical hurdles in that long delays and numerous failures are inevitable. Likewise, it should
not be taken for granted the dangers and negative consequences of nanobiotechnology when
applied in warfare, in the hands of terrorists and disasters associated with its application in
energy generation when and wherever it strikes or the risks associated with nanoparticles in
blood circulation. It should be appreciated that nanotechnology is not in itself a single
emerging scientific discipline but rather a meeting point of traditional sciences like chemistry,
physics, biology and materials science to bring together the required collective knowledge and
expertise required for the development of these novel technologies.

Acknowledgements
The authors wish to express their gratitude to Prof. Guy M. Tremblay and Dr. Jakob Bonlokke
for their critical review of the manuscript and helpful suggestions and also Ms Cecile Bilodeau,
audio-visual department for designing Figure 1.

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Contact Details
Ernest Herbert Rahul Shetty (Corresponding Author)

Department of Medicine Department of Cardiac Surgery

Center for Research Hospital Laval
Hospital Laval 2725 Chemin Sainte Foy
2725 Chemin Sainte Foy Quebec City
Quebec City Quebec G1V 4G5
Quebec G1V 4G5 Canada
Canada
E-mail: [email protected]
E-mail: [email protected] Tel. +1 (418) 656-8711, ext 2653
Tel. +1 (418) 656-8711, ext 2653 Fax. +1 (418) 656-4509
Fax. +1 (418) 656-4509

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