ISSN 1019
3316, Herald of the Russian Academy of Sciences, 2009, Vol. 79, No. 4, pp. 369–377.
© Pleiades Publishing, Ltd., 2009.
Original Russian Text © M.A. Pal’tsev, V.I. Kiselev, P.G. Sveshnikov, 2009, published in Vestnik Rossiiskoi Akademii Nauk, 2009, Vol. 79, No. 7, pp. 627–636.
Review
Nanotechnology is actively penetrating in all spheres of human activity, including medicine. The most prom

ising areas of nanomedicine discussed in the article are pharmacology, diagnostics, tissue engineering, and
surgery. The authors also touched upon the toxicity of nanopreparations. This article is based on a report
delivered at the Nanotechnology International Forum, Moscow, December 3–5, 2008.
DOI: 10.1134/S101933160904008X
Nanotechnology in Medicine
M. A. Pal’tsev, V. I. Kiselev, and P. G. Sveshnikov*
The current stage of medical science opens new
opportunities for penetrating into the vital processes of
the human organism. It is fair to say that the biomolec

ular trend, based on molecular biology, genetics, and
pathology, is now shaping the future of medicine. This
trend deals with new
generation diagnostic and
medicinal preparations and the design of highly effec

tive biosensor systems. The development of nanotech

nology has become a real breakthrough in achieving
the objectives of contemporary medicine.
Nanotechnology is a set of atomic, molecular, or
macromolecular
scale techniques and methods that
ensure the controllable design and use of structures,
devices, or systems in the nanometer range. Such
designs acquire at least one excellent quality or func

tion [1]. The essence of nanomedicine is in using nan

otech achievements to treat (molecular engineering of
medical and diagnostic preparations), diagnose, mon

itor, and control the functions of biological systems
[2].
All countries are trying to develop nanotechnology.
The United States and Japan have implemented the
largest national research programs in nanotechnology.
Global investments in nanotechnology have increased
by an order of magnitude since 1997, reaching $15 bil

lion in 2004 (Fig. 1).
The importance of nanomedicine is obvious. Sci

entific publications on nanomedicine in international
scientific journals have increased four times over the
past decade. Applications for inventions are also grow

ing, indicating the expanding commercialization of
this sphere. The United States is the undisputed leader
in the number of both research publications and
patent applications, producing annually 32% of papers
and 53% of applications; then follow Germany with
* The authors work at the Sechenov Medical Academy, Moscow.
Academician Mikhail Aleksandrovich Pal’tsev (also an acade

mician of the Russian Academy of Medical Sciences) is rector of
the academy. Vsevolod Ivanovich Kiselev, Dr. Sci. (Biol.), is a
deputy director of the Research Institute of Molecular Medi

cine. Petr Georgievich Sveshnikov, Dr. Sci. (Biol.), is chief
research fellow at the Research Institute of Molecular Medicine.
369
8% of papers and 10% of applications and Japan with
9 and 6%, respectively (Fig. 2).
NANOPHARMACOLOGY
The use of nanoparticles for biomedical purposes is
guided by various parameters, such as their nature
(organic and inorganic substances) and physical and
physicochemical (magnetic, electric, optical, and
mechanical) properties [3]. The range of nanoparti

cles that have already found practical applications and
that have a medical potential is very wide. The partic

ular diversity of nanomaterials makes their classifica

tion arbitrary. We find among them
• metallic nanoparticles: superparamagnetic crys

tals of iron, nanoparticles of noble metals (gold and
silver), and semiconductor nanoparticles;
• organic nanomaterials: nanoliposomes, nano

composites from natural materials, and recombinant
synthetic chimeric proteins and peptides;
• carbon nanoparticles: fullerenes and single
and
multilayer nanotubes; and
• synthetic nanopolymers: dendrimers and other
synthetic polymers [1–3].
Table 1 shows the applications and properties of
some nanomaterials.
Nanoparticles have a powerful potential as an effi

cient drug delivery system. Biodegradable (natural and
synthetic polymers and lipids) and metallic nanoparti

cles are used to this end. The main requirements for
nanocarriers are nontoxicity, immunogenicity, and the
ability to carry and release the sufficient amounts of
drugs [13].
Cells capture nanoparticles more efficiently than
larger structures; therefore, nanoparticles are used to
transport and release drugs. Drugs can be integrated
into the particle matrix or attached to the surface of
nanoparticles. The rational development of nanosys

tems is based on knowledge of their interaction with
the biological environment, target
cell population,
and the surface receptors of these cells (taking into
370 PAL’TSEV et al.

Billions of dollars
9

2
1
2
1 3

0
1998 1999 2000 2001 2002 2003 2004

Fig. 1. Investments in nanotechnology in (1) Germany, (2) Japan, and (3) the United States, 1998–2004.
Source: VDI Technologiezentrum, 2006.

account their changing expression during the disease).
The design of such nanosystems must follow the care

ful examination of pharmacokinetics, biodistribution,
and effective accumulation of nanocomposites in the
target organ. The stability and external and internal
distribution of nanoparticles in the biological
microenvironment depend on their chemical nature,
spatial organization, and size [14, 15].
Number of publications and patents
2500
2000
2 evant ligands, corpuscular nanocarriers are targeted at
1500
1 which particles circulate in the bloodstream and
1000
500
0 tive polymers, particularly based on polyoxazoline,
1996 2000 2004
Fig. 2. The number of (1) publications and (2) patents in
nanomedicine, 1996–2004.
Source: VDI Technologiezentrum, 2006.
Nanoparticles introduced intravenously quickly
leave the blood and accumulate primarily in the
Kupffer cells of the liver and in the macrophages of the
red pulp cords of the spleen. This tissue
specific pas

sive clearance reflects the primary role of the immune
system in opposing pathogens. Opsonization with
nanoparticles accumulating on the surface of
fibronectin, immunoglobulins, and complement
sys

tem components serves to recognize and absorb them
with mononuclear phagocytes and dendritic cells.
Nanoparticles are used for the address delivery of
drugs. Therapeutic and diagnostic agents can be
encapsulated, attached covalently to nanocarriers, or
adsorbed on them. Thanks to the small size and func

tionalization, which is achieved by modifying the
nanoparticle surface with synthetic polymers and rel

a certain type of cells and arrive at the assumed com

partment of an organism after systemic introduction.
Surface functionalization increases the time during
avoids nonspecific distribution. Polyethylene glycol
(PEG), which creates the effect of steric stabilization,
is often used as a nanoparticle coating. Its molecules
form a protective hydrophobic layer on the nanoparti

cle surface to prevent particle opsonization by plasma
proteins and particle capture by the cells of the system
of mononuclear phagocytes. Alongside PEG, alterna

polyvinyl ethanol, and polyglycerol, are used as steric
stabilizers [16].
After reaching the assumed compartment, the sta

bilizing coating of nanoparticles in the majority of

HERALD OF THE RUSSIAN ACADEMY OF SCIENCES Vol. 79 No. 4 2009

 NANOTECHNOLOGY IN MEDICINE 371

Table 1. The structural features of nanomaterials and their applications in medicine

Nanomaterials Size Structural features and applications

Superparamagnetic 4–5 nm Hexagonal crystals surrounded by dextran or polyethylene glycol molecules. When
crystals of iron oxide exposed to a magnetic field, these crystals with a high magnetic moment locally vio

late the homogeneity of the field and make possible the lifetime imaging of the as

sumed target. Used for the address delivery of drugs. Functional groups, such as an

tibodies, proteins, and oligonucleotides, can be attached to the surface of iron oxide
crystals [4]
Semiconductor 5–10 nm Formed from cadmium selenide and coated with a zinc sulfide shell, they have
fluorescent metallic unique optical and electronic properties, high quantum yields, and high extinction
nanocrystals ratios. Characterized by a broad band of fluorescence excitation (from the ultravio

let to visible optical spectrum) and a narrow symmetrical band of emission, which,
depending on the nature and size of a nanocrystal, can reside on the assumed spec

trum area. Quantum dots have a unique photostability [5]
Carbon nanoparticles 1–10 nm The third allotropic form of elementary carbon (after graphite and diamond) repre

(fullerenes) sented by fullerenes and nanotubes. These nanoparticles are mainly used to design
nanodevices. Ultimately, they can be used as antibacterial agents, HIV protease in

hibitors, and, after the relevant modification, as a drug depot [6]. Inorganic nano

particles, as a rule, form a nucleus that is coated with a protective layer of inert ma

terial. Functionalization is the modification of the nanoparticle surface to assign
the assumed properties to them. They can be formed by adding structural elements
that recognize molecular targets in vivo or in vitro, such as antibodies, antigens, oli

gonucleotides, etc. [7]
Dendrimers <50 nm Highly luminous polymer macromolecules with a close
to
disperse 3
D structure.
They have a spongy structure, which makes it possible to use them as a matrix. Ther

apeutic and diagnostic agents can be attached to the surface groups of dendrimers
by chemical modification [8]. Polymer micelles are formed in solutions as aggre

gates in which molecular components line up in a spheroidal structure with hydro

phobic nuclei and hydrophilic groups exposed outwardly. Micelles are used for
the systemic release of water
insoluble medical preparations [9]
Nanoliposomes <100 nm Closed single
layer lipid vesicles. Drugs enclosed in liposomes can be delivered to
target organs by modifying the vesicle surface with relevant ligands [10]
Aquasomes 60–300 nm Spherical particles. Used to deliver and release drugs and antigens. The particle nu

cleus is represented by a nanocrystalline calcium phosphate or ceramic carbon and is
coated by an oligomeric polyhydroxyl film. Drugs and antibodies adsorb on the sur

face of these particles [11]
Polyplexes/lipoplexes 100–200 nm Nanostructures that are formed spontaneously between nucleic acids and polyca

tions or cationic liposomes and are used for gene transfection. The polycations most
widely used in gene transfer are poly
L
lysin, linear and branching poly(ethylen

imine), poly(amidoamine), poly
β
amino esters, and cationic cyclodextrin [12]

cases starts to play a negative role, preventing the effi

cient release of drugs. Stabilizer molecules are
attached to the nanoparticle surface with linkers.
Linkers are selected to destroy the connection
between the stabilizing coating and the nanoparticle as
soon as the assumed microenvironment is reached.
Depending on a linker’s nature, the shedding of the
coating can be induced with low pHs, a reduction
reaction, proteolysis, etc. [17].
The address delivery of nanoparticles is carried out
by either passive or controllable transport [18]. The
former ensures the spontaneous accumulation of
nanoparticles that can circulate for a long time in
inflammatory tissues and solid tumors thanks to the
hyperpermeability and retention phenomenon. The
epithelial lining of a pathologically impaired capillary
bed is changed structurally, and fenestrae appear
between endotheliocytes, through which nanoparti

cles can easily penetrate. The absence (in the case of
solid tumors) or deficiency of the lymphatic system,
which is responsible for the drainage of molecules
from healthy tissues, leads to the accumulation of
nanoparticles in pathologically changed tissue [19].
The target delivery of nanoparticles is carried out
by conjugating the relevant ligand with their surface.
Such ligands can be monoclonal antibodies or their
fragments, other proteins, peptides, small molecules,
and aptamers. The ligand’s low affinity is compen

HERALD OF THE RUSSIAN ACADEMY OF SCIENCES Vol. 79 No. 4 2009

372 PAL’TSEV et al.
Table 2. Applications of various nanosystems
Antineoplastic
Nanosystems Antibiotics
drugs
Liposomes + +
Polymers + +
Dendrimers + +
Fullerenes + +
Quantum dots + +
sated by its avidity amplified by increasing the stocking
density on the carrier. Small synthetic peptides, which
are more stable than antibody molecules and, most
probably, nonimmunogenic, are widely used as target
ligands. Carbohydrates, such as lactose, galactose, and
mannose, can also serve as ligands. It is advisable to
use them for marking tumor cells, whose surface has
excessive amounts of lectins.
Recently, aptamers have increasingly begun to be
used. These target selection products of an oligonucle

otide nature have a high affinity and specificity for the
assumed target. They can be viewed as artificial ana

logs of antibodies but of a considerably smaller size
[20]. The design of some carriers is such that they can
be activated by the changing pH of the environment,
chemical stimuli, a rapidly changing magnetic field, or
an external heat source [21]. If modified, carriers can
control the integrity of particles, the release speed, and
the local yield of drugs at the organ, cell, and subcell
levels.
During the address delivery of a drug to the cyto

plasm, nanoparticles have to overcome the endolysos

ome compartment. Nanoparticles from poly
(D,L

lactide
co
glycolide) or nanoparticles with attached
short peptides, like protein transduction domains, are
used to this end. Particles are captured by the recep

tor
independent mechanism of macropinocytosis
through lipid rafts. They are delivered to the cytoplasm
by the chaperonin GroEL E. coli, a heat
shock protein
with nanoparticles (quantum dots) imbedded in it. It
penetrates into the cytoplasm, bypassing the endoly

sosome compartment, and frees a nanoparticle during
ATP binding in the presence of magnesium and potas

sium ions [22].
Nanotechnology opens up opportunities for solv

ing the problem of delivering drugs to brain tumors.
Nanoparticles conjugated with the lectin Ulex
europeus effectively overcome the hematoencephalic
barrier [23].
Multifunctional nanocarriers have also been cre

ated to simultaneously carry a drug, a ligand responsi

ble for address delivery (for example, antibodies or
aptamers), and a contrast agent. Such nanoparticles
can be used to release specific antitumor preparations,
identify circulating tumor cells, and monitor treat

HERALD OF THE RUSSIAN ACADEMY OF SCIENCES
Genetically
Immunomo

Peptides engineered Vaccines
dulators
preparations
+ +
+ + + +
+ +
+
ment efficiency in real time. The behavior of nanopar

ticles in the biological microenvironment and their
stability and extracellular and intracellular distribu

tion vary depending on their chemical nature, spatial
structure, and size [24]. Liposomes and micelles have
the potential to deliver drugs to tumors, since the use
of such nanocarriers reduces drug toxicity, sets the
time parameters of their release, and modifies the
pharmacokinetics and biodistribution of preparations
[25, 26].
Nanoparticles help overcome multiple drug resis

tance by delivering cytostatics to tumor cells without
launching the glycoprotein pump. The strategy of
overcoming drug resistance is based on the use of new
drug release systems that ensure selective drug accu

mulation in tumor tissues, tumor cells proper, or even
in their cytoplasmic compartments. Doxorubicin

loaded particles from poly(alkyl
cyanoacrylate) can
penetrate into cells without being recognized by p
gly

coprotein. Clinically, drug resistance under AIDS

associated Kaposi’s sarcoma was overcome due to the
use of doxorubicin enclosed in liposomes [27].
Nanocomposites have been designed for the simul

taneous target delivery of a preparation, target imag

ing, and target destruction. Biodegradable natural
polymers (albumin, chitosan, and heparine), designed
to carry various drugs, such as antitumor preparations,
antibiotics, and protein preparations, including vac

cines, genetically engineered drugs, and immuno

modulating preparations, are increasingly often used
as nanocontainers for drug delivery [28]. The possibil

ity to include any particular substances into various
classes of nanoparticles has been proved (Table 2).
NANODIAGNOSTICS
In the majority of nanodiagnostic tests, the nano

probe is connected to the target molecule, which
ensures the recording of the biomolecular target’s sig

nal. For noninvasive diagnostic tumor imaging in vivo,
liposomes and micelles are the most promising nano

carriers of contrast agents. In liposomes, contrast
agents can be incorporated both into the internal water
compartment and into the membrane to be used in
gamma and magnetic resonance imaging. If metallic
Vol. 79 No. 4 2009
 NANOTECHNOLOGY IN MEDICINE
nanoparticles serve as contrast agents, the reporter
metal can be chelated into diethylenetriamine and
integrated into liposomes [29]. To obtain the strongest
signal during magnetic resonance imaging, all reporter
atoms are dislocated to contact the water phase.
Polychelating amphipathic polymers with the main
chain and multiple lateral chelating groups have been
synthesized. These polymers can bind multiple atoms
of the reporter metal and hydrophobic end groups that
amplify polymer adsorption on hydrophobic nanopar

ticles or liposome or micelle incorporation into the
hydrophobic domains. As a result, the number of car

rier
bound reporter
metal atoms and the intensity of
the imaging signal increase manifold. This approach
has been successfully used for the in vivo magnetic res

onance detection of the lymphoid system compo

nents. Gadolinium
loaded nanocarriers were used to
identify tumor metastases in lymph nodes. Dextran

coated superparamagnetic nanoparticles of iron oxide
are used for the same purpose in prostate cancer
patients. This method helped identify microme

tastases of less than 2 mm in size. Indium
111
labeled
long
circulating liposomes are used to diagnose lung
cancer, head and neck carcinoma, AIDS
associated
Kaposi’s sarcoma, skin cancer, glioblastomas, and
metastatic brain tumors, as well as soft tissue sarcoma
[30, 31].
The molecules of imaging agents and tumor
spe

cific ligands can be built into the same nanoparticle.
Multivalent magnetic nanocrystals bound with the
tumor
specific antibodies Herceptin are successfully
being used for in vivo cancer diagnostics by magnetic
resonance.
Simultaneous imaging of tumor cells and photody

namic near
infrared laser therapy are possible with the
use of high
adsorption gold nanorods. In addition,
these nanoparticles scatter electromagnetic radiation.
Diagnostic systems that record fluorescent signals
prefer the use of quantum dots conjugated with anti

bodies, oligonucleotides, and aptamers or coated with
streptavidin. Since quantum dots are water insoluble
and toxic, they are coated with water
soluble ligands
or encapsulated into phospholipid micelles, polymer
beads, or amphiphilic polysaccharides. Quantum dots
also find application in immunohistochemical bioptic
analysis [32].
Nanocrystals can be a basis for the main supersen

sitive noninvasive methods of imaging preceptor mol

ecules and disease markers of various etiologies. In
cardiology, nanotech molecular imaging in vivo makes
it possible to record destructive changes in atheroscle

rotic lesions by detecting fibrin on their surface with
ultrasonic and magnetic resonance scanning [33]. The
diagnostics of intravascular microthromb formations
and inflammation under atherogenesis is conducted
with liposomes whose address delivery is carried out by
the ligands of intercellular and vascular cell adhesion
molecules (ICAM
1 and VCAM
1), fibrinogen, and
HERALD OF THE RUSSIAN ACADEMY OF SCIENCES
373
the tissue factor. Superparamagnetic nanoparticles
carrying a ligand for apoliprotein E were used in mag

netic resonance imaging of VCAM
1 in the aorta
endothelium [34]. Molecular imaging in vivo allows us
not only to localize pathological processes but also to
record the level of expression and activity of specific
molecules and to assess biological processes (apopto

sis, angiogenesis, etc.) that influence the development
of pathologies and response to therapeutic interven

tion [35].
Nanotechnology considerably improves the analy

sis efficiency and opens new opportunities for testing
biological molecules whose sizes vary in the nanome

ter range. The advantage of nanotesting is supersensi

tive, automatic, and fast detection in the absence of
preliminary cleaning of biomaterial. Nanotests are
widely used to analyze molecules of nucleic acids and
proteins.
A nanobarcode method has been developed to
detect a wide range of biomolecular targets in biologi

cal fluids [36]. Nickel nanorods are crosshatched with
gold and silver strips, and detector molecules (anti

bodies or oligonucleotides) are attached to them.
Thus, an individual bar code can encode a detectable
object bound to it. A change in the optical properties
of a bar code indicates the presence of a detectable
molecule in the sample under study [37].
Nanobarcodes help identify genetic defects, which
arise from point mutations of a gene owing to the
replacement of a single nucleotide. Nanobarcode

based analysis may be viewed as an alternative to the
polymerase chain reaction.
Clinically, nanobarcodes are used to diagnose pros

tate cancer and Alzheimer’s disease, as well as various
infections.
Cantilevers, like those used in atomic force micros

copy, help analyze DNA samples. They are used in
DNA hybridization. DNA fragments capable of bind

ing a complementary DNA target are applied to the
cantilever surface (beam nanostructures on a solid
substrate). During sample scanning, the target DNA
sequence is hybridized with the cantilever’s single

stranded DNA, which leads to mechanical deforma

tion of the sample, and the extent of deformation is
proportionate to the amount of DNA hybridized. The
deformation is recorded by optical or electromechan

ical signals. This approach can be used in microchips.
In this case, the cantilever surface is coated with
monochannel antibodies or aptamers. Cantilevers
help identify tumor
associated antigens, infectious
agents, and the myocardium damage marker tropo

nin, as well as acetone and dimethylamine in exhaled
air [38–40].
Quantum dots are suitable for multiple spectral
coding of protein cells. Sets of quantum dots with
assumed fluorescence spectra are enclosed in polymer
microspheres to which biotarget
specific molecules
Vol. 79 No. 4 2009
374 PAL’TSEV et al.
(monochannel antibodies or complementary oligonu

cleotides) are attached covalently. The code of a
microsphere is determined by the combinations of
colors of nanocrystals enclosed in it. Such micro

spheres help detect and analyze the composition of
complex protein or nucleotide mixes [41].
Oligonucleotide
modified nanoparticles of gold
are used to image and quantify DNA in living cells. A
new class of probes (nanoflares) has been designed to
identify and quantify mRNA in living cells. The prin

ciple of their use is based on the unique optical prop

erties of gold nanoparticles, powerful dissipators of
fluorescence. Gold nanoparticles, functionalized by a
recognizing oligonucleotide sequence, hybridize with
a short complementary reporter sequence that carries
fluorochrome Cy5. In the bound state, the Cy5 fluo

rescence of the reporter sequence is dissipated due to
the closeness of the nanoparticle surface. In the pres

ence of an mRNA target, the reporter sequence dis

unites with the nanoparticle. As a result, a long and
stable duplex is formed between the target and the
nucleotide
modified nanoparticle, which leads to a
sharp amplification of the fluorescent signal, a flare.
Such nanoprobes can be used not only for mRNA
detection but also for transduction, as well as for the
assessment of its efficiency [42].
Molecular antennae, or genetically coded fluores

cence resonance energy transfer (FRET) nanosensors,
are used for the fine analysis of biological processes in
vivo. The FRET phenomenon means the transfer of
energy between two chromophores (the donor and the
acceptor), whose emission and absorption spectra
overlap. Energy transfer strictly depends on the dis

tance between the donor and the acceptor, which
allows us to trace the process of intermolecular inter

actions. Such sensors are already used to detect
glutamate release by neurons, as well as to assess
glutamate metabolism and transport in glia cells and to
detect neuronal activity intravitally [43, 44]. To mea

sure the level of glucose in the human blood serum, a
FRET nanosensor has been designed on the basis of
energy transfer from CdTe quantum dots conjugated
with concanavalin A (donor) to Au nanoparticles
modified by thiolated β
cyclodextrins (acceptor).
Glucose competes with β
cyclodextrins for the bind

ing sites of lectin (concanavalin A), which leads to the
allosteric modification of sensor components and the
generation of a fluorescent signal [45].
TISSUE BIOENGINEERING: TISSUE
REGENRATION AND REPLACEMENT
Tissue engineering strategy implies the isolation of
cells from the organism followed by their in vitro
expansion and seeding on a 3
D biodegradable sub

strate. The latter serves as a structural matrix and res

ervoir for active molecules, such as cytokines and
growth factors. The substrate disintegrates with time in
HERALD OF THE RUSSIAN ACADEMY OF SCIENCES
the patient organism, being displaced by the healthy
implant tissue. The substrate is constructed from
nanofibers that mimic the structure of natural tissues
on the nanometer scale. The high surface
to
volume
ratio of nanofibers in combination with their
microporous structure ensures cell adhesion, prolifer

ation, migration, and differentiation.
Nanomatrices are formed from natural and syn

thetic polymer materials [46]. The advantage of the
former is the similarity and often identity to macro

molecular substances represented in the organism.
The natural material usually used is collagenous
nanofibers from which myoblasts and chondrocytes
are successfully grown [47, 48]. Thanks to the cross

linking of nanothreads of type II collagen, matrices
from this biomaterial have a high mechanical strength.
The same is typical of the nanofibrils of type I collagen
modified by polyethylene oxide [49]. The nanoparti

cles of another natural polymer, chitosan, form in
combination with polyethylene oxide a matrix suitable
for growing osteoblasts and chondrocytes [50]. The
natural component of a territorial matrix, hyaluronic
acid, as well as gelatin in combination with poly(ε

caprolactone), silk fibroin, and tropoelastin nano

threads are successfully used to design tissue matrices
[51].
Synthetic polymer materials, such as polylactic
acid and poly(ethylene terephthalate), are used to
design blood vessels; poly(ε
caprolactone), to regen

erate nervous and cartilaginous tissues; and poly(1

lactid
co
ε
caprolactone) serves a territorial
matrix
biomimetic for smooth
muscle and endothelial cells
[52]. Polylactic coglycolic acid is a polymer widely
used to obtain nanofibers for bone and cartilaginous
tissue design and for controllable drug release [53].
Carbon and aluminum nanofibers are used as bioma

terials to produce dental and orthopedic implants.
Bone matrices are formed from polymer inorganic
composites (for example, PLLA
hydroxyapatite) with
improved osteoconductivity and mechanical proper

ties [54].
The deficit of endogenous signal molecules, neces

sary to repair major tissue defects, replenishes growth
and differentiation factors. Techniques have been
developed to immobilize nanospheres that carry signal
molecules in the matrix cavity [55].
NANOSURGERY
The objects of nanosurgical intervention are cells
and subcellular structures (organelles, chromosomes,
the cytoskeleton, etc.). Nanosurgery also helps to
actively intervene in the vital processes of cells.
Methods have been developed to assess the local

ization, transport, and interactions of molecules in liv

ing cells. Magnetic forceps are used to study the
behavior of individual micromolecules and to relocate
small magnetic nanoprobes in living cells [56]. Optical
Vol. 79 No. 4 2009
 NANOTECHNOLOGY IN MEDICINE
forceps (trap) allow us to manipulate microscopic
objects with the help of a laser beam, transmitted by a
laser diode. Laser forceps, based on optic fibers, help
separate malignant cells from healthy ones, as well as
sort cells by the method of fluorescent flow cytometry
[57, 58].
Nanosurgical instruments find use in cellular tech

nology. Genes are transfected into living cells with
ultrathin ceramic nanoneedles in atomic force
microscopy [59]. A minimally invasive technique of
transferring genes into human mesenchymal stem
cells has been developed to obtain a highly efficient
expression of the transfected gene [60]. A femtosec

ond laser microscope was used to transfect genes into
the stem cells of the human pancreatic and salivary
glands [61]. A femtosecond laser is also used success

fully to cut off assumed genome sections with a high
resolution (6.5 × 104 base pairs of chromosomal DNA)
and without disrupting cell viability [62].
***
A problem that may limit the wide use of innova

tion nanobiotechnology is the toxicity of nanoparti

cles. The translation of various materials into the
nanometer band often presents radical changes in
their properties [63, 64]. Therefore, nanoparticles can
adversely affect biological systems. In addition,
genetic polymorphism can make part of a population
abnormally sensitive to the effect of certain classes or
types of nanoparticles. This necessitates the develop

ment of new methods of preclinical safety evaluation
of nanopreparations [64, 65].
This complex problem requires the efforts of toxi

cologists, physicists, chemists, materials scientists,
medical doctors, molecular biologists, and specialists
in bioinformatics. The international Nanotox 2008
conference announced the creation of an interdisci

plinary community of scientific experts, International
Alliance for NanoEHS Harmonization (IANH),
whose goal is to prepare protocols for reproducible
toxicological testing of nanomaterials in vitro and in
vivo.
At present, we see rapid growth of nanomedical
technologies. According to analytical companies, 16%
of medical goods will be nanotech derivatives by 2014.
The sales of materials for use in nanobiotechnology
yielded $750 million in 2004. It is anticipated that by
2011 the incomes will reach $2 billion. Venture funds
channel capital into nanotechnology, 52% of $900

million venture capital already injected in nanotech

nology between 1999 and 2003 coming from new
entrants.
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