34 Recent Patents on Biomedical Engineering 2008, 1, 34-42

Use of Core/Shell Structured Nanoparticles for Biomedical Applications

Nagarajan Sounderya1 and Yong Zhang1,2
1
Division of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore 117574, Singapore,
2
Nanoscience and Nanotechnology Initiative, National University of Singapore, Singapore 117576, Singapore

Received: October 30, 2007; Accepted: November 9, 2007; Revised: November 16, 2007
Abstract: Nanoparticles have found wide spread application in varied fields of engineering. Recently, core/shell
nanostructures have been found to have improved properties when compared to their other alternatives are patented. These
core/shell structures also interest researchers in the field of biomedical engineering and some potential applications have
been identified. The classification of core/shell nanoparticles, the synthesis of these structures and their applications in the
field of biomedical engineering are discussed in this article. The future work points at the possibilities of improvement
and the material that might be preferred for specific applications.
Keywords: Core/shell, nanoparticles, biomedical applications, nanoparticles synthesis.

INTRODUCTION position. This rule is applicable to core/shell nanoparticles

and hence, we try to classify them broadly based on the
“Small is beautiful”, today we know that small is not
material with which the core and shell of the nanocomposite
only beautiful but also powerful. With the range of
are made. On these lines we can group the nanoparticles as
applications that nanoparticles find in varied fields of engi-
neering and science, nanoparticles seem a promising option 2.1. Inorganic Core/Shell Nanoparticles
when compared to the conventional materials used.
The core or the shell or both are made of inorganic
Nanoparticles are particles that have at least one dimension
materials. The inorganic materials in most commercially
in less than 100nm range. They have a high surface to
used and widely synthesized nanoparticles are metals,
volume ratio and thus mass transfer and heat transfer
semiconductors or lanthanides.
properties are better than bulk materials. Recently; core/shell
nanoparticles are finding widespread application. There is a 2.1.1. Metallic Nanoparticles
class of core/shell nanoparticle that has its entire constituent
The core or the shell should contain metallic component.
in the nanometer range.Core/shell nanoparticles are nano-
The core of such structures can be a metal or metal oxide or
structures that have core made of a material coated with
inorganic like silica while the shell can also be any inorganic
another material. They are in the size range of 20nm-200nm.
material like silica or can be a metal or metal oxide. The
Also, composite structures with these core/shell particles
most widely used core/shell nancomposites are gold or silver
embedded in a matrix material are in use. The necessity to
shift to core/shell nanoparticles is the improvement in the core with silica shell. The gold/silica nanoparticles find
application in optical sensing and the thickness of the silica
properties. Taking into consideration the size of the
coat alters the optical property of gold nanoparticles.The
nanoparticles, the shell material can be chosen such that the
silica coat makes the gold nanoparticles biocompatible [4,5].
agglomeration of particle can be prevented. This implies that
The silver/silica particles can be used in fluorescence
the monodispersity of the particles can be improved. The
imaging and again the region of emission is dependent on the
core/shell structure enhances the thermal and chemical
stability of the nanoparticles, improves solubility, makes silica coating thickness. The structure can be inversed and
silica nanoparticles can form the core and the gold can form
them less cytotoxic and allows conjugation of other mole-
the shell. The thickness of the gold coat can be varied and a
cules to these particles. The shell can also prevent the oxida-
range of colors can be obtained. These particles find
tion of the core material [1,2]. “When a core nanoparticle is
application in fluorescent bioimaging. Metal interaction with
coated with a polymeric layer or an inorganic layer like silica
the fluorophores increases photo stability, enhances fluore-
because the polymeric or inorganic layer would endow the
hybrid structure with an additional function/property on top scence, reduces lifetime. Also fluorescent core/shell nano-
particles enhance single particle imaging. Other core/shell
of the function/property of the core hence synergistically
nanoparticles that find application in optical bioimaging are
emerged functions can be envisioned” [3].
copper/copper oxide [6] and these fall into the category of
2. CLASSIFICATION OF CORE/SHELL NANO- metal/metal oxide nanoparticles. Magnetic imaging for
PARTICLES biological applications is the trend of the day and particles
that cater to these needs are iron oxide/silica, iron oxide/gold
The properties of the nanomaterials are diverse and nanocomposite [7-11]. The former is a metal oxide/inorganic
cannot be generalized even though the particles under
nanocomposite while latter is a metal oxide/metal nanocom-
comparison might be made of similar material and com-
posite. The gold coating on iron oxide makes it microchip
compatible and the silica coat prevents agglomeration and
*Address correspondence to this author at the Division of Bioengineering,
Faculty of Engineering, Block E3A-04-15, National University of
also enables conjugation. Some other core/shell nanopar-
Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore; Tel: +65- ticles in this category include tin/tin oxide nanoparticles [12]
65164871; Fax: +65-68723069; E-mail: biezy@nus.edu.sg that are used in food processing and humidity sensor, gold/

1874-7647/08 $100.00+.00 © 2008 Bentham Science Publishers Ltd.

Use of Core/Shell Structured Nanoparticles for Biomedical Applications
palladium core/shell structure which are used as catalysts
[13].
2.1.2. Semiconductor Nanoparticles
These types of nanoparticles have core made of semi-
conductor material, semiconductor alloy or metal oxide with
shell made of semiconductor material, metal oxide or
inorganic material like silica [14]. These structures can be
binary with a core and shell or a tertiary structure with a core
and two shells. The most common binary structure that are
well known by the name quantum dots are an alloy of group
3 and group 5 metals or group 4 and group 6 metals.
CdSe/Cds, CdSe/ZnS, ZnSe/ZnS, CdTe/CdS are the nano-
particles used for fluorescent bioimaging [15]. The shell
thickness determines the emission range of these particles.
They fall under the category of binary nanoparticles. The
CdSe/CdTe core/shell nanoparticles are stable and have high
conductivity. Addition of acceptor ions such as bipyridium to
CdSe/Zns or similar nanoparticles can enhance the fluore-
scence properties [15-23]. Mechanical properties can be
improved by adding high performance polyamines and
polypyrroles [19,20]. The electronic properties can be
enhanced and size tunability of quantum dot nanoparticles
depends on the matrix material. Nanoquantum dots can be
dispersed in Titania matrix and they have better lumine-
scence than the quantum dots in sols. Quantum dots have
magnetic property when the core shell structure has Co/Cd or
Cd/Co [21,24,25]. There are complex structures such ZnS,
ZnxCd1-xS in PMMA matrix which show variation in lumine-
scence on varying Zn/Cd ratio [26]. There are also tertiary
structures that have magnetic property such as iron oxide/
CdSe/ZnSe [18,24]. These are bifunctional having both
fluorescence and magnetic properties. Thus detailed in vivo
imaging is possible.
2.1.3. Lanthanide Nanoparticles
These particles core which contains one or more
lanthanide group elements surrounded by a shell made of
inorganic material like silica or a lanthanide material.
Rhabdophane lanthanide phosphate aqueous colloids are one
of these categories that show a green luminescence. These
are Ce; Tb doped core particles with an LnPO4-xH2O shell
[21,27,28]. These particles can be further coated with silica
to enhance its luminescent properties. These find potential
application in electronics and bioimaging. Other lanthanide
particles include YF3 /Silica, TiO2: Eu phosphors and the
like. The YF3 particles show emission in the range of 400nm
and TiO2/Eu phosphors show a red emission peak. The
potential application of these particles is in the field of
bioimaging [29].
2.2. Organic-Inorganic Hybrid Core/Shell Nanoparticles
2.2.1. Organic core and Inorganic Shell Nanoparticles
The core of these particles consists of organic com-
pounds and can be polymers of organic compounds. The
shell is inorganic and is a metal or silica or silicone.
Structures that fall under the category of polymer/metal are
polyethylene/silver, polylactide/gold [19,30-38]. These are
used in joint replacements and due to their high resistance to
corrosion and abrasion can be used to improve properties of
other materials. Many of these nanoparticles manufactured
Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1 35
fall under the category of polymer/silica and some of them
are polycaprolactum/silica, polystyrenemethylmethacrylate/
silica [4,39-47].
2.2.2. Inorganic Core and Organic Shell Nanoparticles
The particles in this class of nanoparticles have a metal,
metal oxide or silica core with a polymer of organic material
or organic shell. Some of the particles in this category are
SiO2/PAPBA(Poly(3-aminophenylboronic acid) [48], Ag2S/
PVA(Polyvinylalcohol), CuS/PVA, [49,50] Ag2S/PANI(Poly
aniline) [51,52], and TiO2/cellulose. The coat of PAPBA
prevents agglomeration of particles and helps maintain size
control.SiO2/PAPBA is used in optical devices, sensors and
electrical devices. The PVA or PANI coat prevents oxidation
of Ag2S /CuS thus improving stability. Ag2S /CuS are con-
ducting polymers [41,53] that are used in electrical industry.
The addition of cellulose improves the pigment properties of
TiO2.Some of these hybrids find application in dentistry as
brace material and fillers.
2.3. Polymeric Core/Shell Nanoparticles
These are particles that have a polymeric core and a
polymeric shell and are dispersed in a matrix which can be
any material whose property is to be modified. One of the
materials in this category is Polymethylmethacrylate
(PMMA) coated antimony trioxide compounded with Poly-
vinylchloride (PVC)/antimony trioxide composites [54]. The
interaction between PMMA and the PVC along with
antimony trioxide enhance toughness and strength of PVC.
Some of these particles improve the thermal sensitivity of
materials [55,56]. Polystyrene/Poly(N-isopropylacrylamide)
(P-NIPA) core/shell nanoparticles with silver embedded in
the NIPA coat are found to enhance the catalytic activity of
silver by improving sensitivity. In the field of electronics the
sensitivity to voltage change is improved by using junctions
such as (poly-(3, 4 dicyanothiophene) PDCTh / (methoxy-5-
(2’-ethyl-hexyloxy)-1, 4-phenylene vinylene) MEH-PPV
[57,58]. Phase segregated nanoparticles blend of donor
(MEH-PPV) and Cyano substituted phenylene vinylene (CN-
PPV) show enhanced photo induced charge separation. Some
of the other composite latexes that find application are
PSt/PVAc, PSt/Ppy and PSt/PBA where PSt is polystyrene
[59,60]. PVAc is polyvinyl acetate, Ppy is polypyrrole and
PBA is poly butyl alcohol [61,62].
3. SYNTHESIS OF CORE/SHELL NANOPARTICLES
The most commonly used technique has been discussed
and we have tried to generalize the type of particle that can
be synthesized by each of these methods. Though it is not a
rule that is applicable to all cases but it can be applied to
most cases [63-68].
3.1. Polymerization
3.1.1. Radical Polymerization
The polymerization could be a free radical polymeri-
zation or an atom transfer radical polymerization. The
process of atom transfer radical polymerization (ATRP) is
better than the free radical polymerization as control of
molecular weight and size of the particle can be achieved.
The coating of polymer on silica nanoparticles is generally
done by ATRP. The surface of the silica particle is modified
36 Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1
DMAEMA
CuBr
Initiator 2,2’-dipyridyl
RT, water
Initiator = ( S(CH2) 11OOCC(CH3)2Br)2
Fig. (1). Schematic Representation of Procedure (Reprinted with permission from Kang et al. Copyright 2006. Institute of Physics
Publishing).
with a suitable initiator. One of the methods would be to
attach a bromine group to the surface of silica and add to
solution containing the monomer of the shell polymer. The
polymerization occurs and is depicted by change in the
optical clarity of the solution. This method of attachment of
bromine group to silica and forming polymer of t-butyl
acrylate has been discussed by lei et al. [69]. Also Kang et
al. [3] discuss the formation of silica coated gold nanopar-
ticles by a biomimetic approach through ATRP.
3.1.2. Chemical Oxidation Polymerization
The nanoparticle, if it has suitable groups attached to it
allows the monomer which are generally aromatic com-
pounds to form adduct. The monomer can be polymerized by
adding suitable oxidizing agents. Generally metallic particles
are given a coating of poly aromatic compounds by this
method. Most metallic nanoparticles are formed by chemical
reaction and then reduction. This implies there might be
acidic or basic groups attached to the surface that induces
modification [70,71]. Such a method has been discussed by
Jing et al. [51,52,72] in silver/poly aniline and silver/poly
pyrrole and PbS/poly pyrrole core/shell nanocomposite
synthesis [73].
3.2. Sol Gel Method
This method of synthesis is used generally for the
synthesis of metal/polymer core metal oxide shell nano-
particles in inorganic matrix that forms a gel, like silica. But
some semiconductor nanoparticles have also been synthe-
sized by this method [74,75]. The steps can be stated in
general as formation of the solution containing the salt of the
metal and silica based compound. The solution is then heat
treated and upon gelation, the metal salt is reduced in
hydrogen atmosphere to metal nanoparticles. These are then
subjected to heat in ordinary atmosphere forming an oxide
shell on top of the metal nanoparticles. For polymer core and
metal oxide shell the polymer nanoparticles can be added to
metal salt solution and then oxidized. Iron/iron oxide,tin/
tinoxide,copper/copper oxide in silica matrix have been
synthesized by this method [12,76-78]. There is some refe-
rence to synthesis of polypyyrole/iron oxide nanoparticles
[35] and Cdse/CdS nanoparticles by this method [19].
3.3. Reverse Micelle Method
One of the major concerns in the synthesis of nano-
particles and in specific core/shell nanoparticles is the
achievement of control over size and morphology. This can
be obtained by conducting the synthesis in emulsions or in
Sounderya and Zhang
Silicification
solutions that form micelles. Micelles are formed by mixing
aqueous reactant with suitable surfactant. Micelles act as the
center for nucleation and epitaxial growth of nanoparticles.
The molar ratio of the surfactant to water (
) is the
parameter that affects size and morphology of the resultant
particles. These particles can be further processed to obtain
core/shell structure by oxidation polymerization as discussed
above. Else the surface can be coated with other metals or
silica [79,80]. Carpenter et al. [81] have discussed reverse
micelle technique for the synthesis of iron nanoparticles with
a gold shell. Similar method has been proposed for cobalt-
platinum core/shell structure by Kumbhar et al. [82].Wang et
al. [83] discuss iron oxide with gold core but have used
ligand exchange reactivity to assemble particles into thin
films. Polymeric particles can also be synthesized if the
emulsion of the monomer is thermodynamically stable [84-
87].
3.4. Mechanochemical Synthesis
The above discussed sub-topics themselves give an idea
about the process to the readers. This sub-topic in itself
houses varied synthesis techniques of which only two com-
monly used ones will be touched upon here. Mechano-
chemical synthesis as the name suggests involves mechanical
and chemical means of nanoparticle synthesis.
3.4.1. Sonochemical Synthesis
The synthesis involves chemical reaction for nanoparticle
synthesis and sonication to improve the speed of reaction,
breakdown the particles and to enhance the dispersion of
particles in the solvent. Ultrasonic irradiation of the
frequency range 20 kHz to 1 MHz has been used in most of
the sonication methods. Ultrasonic irradiation speeds up the
reaction because of the localized cavities that are formed and
they last only for a short time. Thus, these cavities act as
micro reactors for the reaction to occur and the mechanical
effects to also take place. The mixture of reactants in suitable
solution is subjected to ultrasonic waves and the temperature
and pH maintained to obtain the nanoparticles dispersed in
silica or in matrix material. The chemical reaction that
occurs depends on the shell required as core is synthesized
separately and added to the reactant mixture. Reduction
reactions are carried out for metallic shells and in situ
polymerization for polymeric shells/non-metallic shells [87-
89]. Composites such as iron oxide with gold shell and
iron/cobalt alloy nanoparticles are ones with metallic shell
[11] and those such as silica/PAPBA,Ag2S/PVA,CuS/PVA
Use of Core/Shell Structured Nanoparticles for Biomedical Applications Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1 37

Highly ordered nano-arrays of titania-based nanohybrids by copolymer terplating

PMMA PEO

Micelles formation
in a mixture of THF
(a) and H2 O

Selective uptake of hydrochloric Structural arrangement and growth

acid and titanium alkoxide into of TiO nanoparticles during thin film
hydrophilic PEO domains formation and annealing process

(b) (c)

50 nm 50 nm

200 nm 200 nm

Fig. (2). Assembly of Titania Hybrid and TEM Pictures (Reprinted with permission from J Wang and AH Yuwono. Copyright 2006.
Engineering research News NUS).

are ones with nonmetallic shell that are synthesized by this
method [11,22,49,90].
3.4.2. Electrodeposition
Formation of shell of nanoparticles with charged
polymers or inorganic material can be carried out by this
method. The electric pulse is varied like a square wave in
general and it is found that the metal deposits during
negative cycle while polymer deposits during positive cycle.
This gives control over the size of the nanoparticles. The
mode of operation is galvanization hence, the deposition
occurs on one of the electrodes. The matrix material for
nanoparticles can be the electrode or the electrolytic
medium. Banerjee et al. [7] detail on the synthesis of iron
oxide shell iron in silica nanoparticles. Chipara et al. [35]
describe the synthesis of polypyyrole-iron nanoparticles.
Both the procedures are almost similar, the only difference
being that in the iron oxide shell iron in silica nanoparticles,
the electrolytic medium, silica gel, is the matrix for the
nanocomposite while for the PPy-Fe,it doesn’t have a matrix
material and belongs to the class of nano-nanoparticles.The
PPy-Fe can be dispersed in the desired matrix material later
[30].
Some other methods of synthesis include mechanical
attrition, colloidal chemical synthesis, layer deposition and
the like which are used widely for synthesizing magnetic
nanoparticles. Some copper oxide nanoparticles are synthe-
sized by reduction and pulverizing [68,91].
4. BIOMEDICAL APPLICATIONS AND PATENTS
Core/Shell Nanoparticles are finding wide spread
applications in all fields. They are making their way into our
day to day life. Things such as cabinet and car doors contain
nanoparticles which improve their durability. At a large scale
the industries that make most use of these materials are the
chemical, electronics, biomedical, civil and mechanical
Industries. They are used as catalysts, modifiers, fillers, ther-
mal and mechanical property enhancers, sensor material due
to high sensitivity to slight changes in parameter. The bio-
medical industry is the potential play field today; hence some
of the possible application will be highlighted. Some of these
applications are patented and some are still in the research
phase [92]. The diverse branches of the industry where
nanoparticles are being recognized are bioimaging, drug
delivery, biomarkers and transplants.
4.1. Bioimaging
The imaging modalities in which core/shell nanoparticles
are used are MRI and luminescence. Magnetic nanoparticles
iron oxide or cobalt core particles are used to enhance MRI
images by improving contrast. Core/shell nanoparticles can
enter the cells and they have better spin-lattice relaxation
time. Thus the contrast is better [10,20,35,78,82,93-95].
These particles are found to be biocompatible, so they seem
very promising. The luminescent particles are particles that
fluoresce by absorbing light over in a wavelength range and
emit in the visible or near-IR range. The nanoparticles with
38 Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1 Sounderya and Zhang

Electrooxidative
polymerization
Reference N
electrode N in scCHF3 medium n
Working
500 mA cm-2
electrode

Counter
electrode
scCHF 3

-0.4 0 0.4 0.8 1.2

Potential /V vs. Ag wire

Fig. (3). Electrochemical Synthesis of Nanoparticles (Reprinted with permission from Atobe et al. copyright 2004. The Chemical Society of
Japan).

NIR region emission are still being worked on as the cells do

not emit in the same range. Thus signal to noise ratio is high.
Though they cannot be easily applied to in-depth live cell
imaging, the application is not impossible. Similarly particles
that emit in the UV-visible range sometimes have low signal
to noise ratio. But the composition and particle size can be
varied to get appropriate emission and detection is also a lot
easier. The present trend are the up conversion nanoparticles
which show anti-stokes emission and these are brighter than
down conversion nanoparticles that show stokes emission.
C D
The ranges of nanoparticles that are luminescent are
semiconductor nanoparticles, lanthanide based nanoparticles,
and gold coated silica nanoparticles and the like [18,20,
21,23,27,29,78,96-98]. Multifunctional nanoparticles that
have magnetic and luminescent properties can also be
synthesized by choosing appropriate core and shell [99]. This
helps in obtaining clear 3D images.
4.2. Drug Delivery A B

Core/Shell structures serve a wide category of drug

delivery application. The particles are biocompatible, have
the ability to be conjugated to molecules without affecting
the core and also can be used to encapsulate drugs [100]. The
material of choice decides the multifunctional nature of the
particles [21]. They can be structured so that they can be
used for imaging and for drug delivery. Drug eluting stents
made of nanocomposite material [101,102] are being worked
upon to reduce abrasion and also core/shell nanoparticles
with antibacterial properties are also being worked upon
[103]. The latter seems promising for the manufacture of
catheters which shall reduce infections that are caused by
catheter contamination. The drugs can be targeted to specific
locations by attaching biomolecules such as antibodies to the
surface of nanoparticles.This is very useful when it comes to
targeting tumor cells. Thermo sensitive and pH sensitive
nanoparticles can be used for environment controlled
delivery of drug from the particles [71]. Bifunctional
nanoparticles with a luminescent core and shell conjugated
with a biomolecule/drug that can be used for targeting /drug
delivery and imaging. Drug loaded contact lenses are an
elucidation of how these materials can be used for
encapsulating drugs [104-107].
Fig. (4). Uptake of Nanoparticles by 143B Osteosarcoma Cells. A)
Detection of Texas Red Labeled Nanoparticles, B)Bright Field, C)
Detection of DAPI and D) Overlap of these Three Images (
Reprinted with permission from Azarmi et al. copyright 2006.
Canadian Society for Pharmaceutical Sciences).
4.3. Cell Labeling
Nano biomarkers will be more efficient as they can
operate at wide pH and temperature ranges. They are small
and can penetrate through cells and even if they do not
penetrate they can be targeted to specific cells by attaching
suitable moieties to the shell surface. The wide color range
that these particles display on varying shell thickness and
their photo stability are also important characters that make
them suitable for marking/cell labeling [108]. Nanocompo-
site biomarkers are used for labeling cancer cells [20,109,
110] and tumor cells. There can be multifunctional particles
that act not only as markers, but also can be used for cell
separation, if the core of the particle has magnetic properties.
Use of Core/Shell Structured Nanoparticles for Biomedical Applications Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1 39

NHCOCH 3
O O
OH OH
HO HO
NHCOCH3 O
. CH CH CH2OH
NH3 OOC
HO OH HO OH
OH HO O
COO- ‘H N
HOH2C C CH 3
O
H O
OH
OH
HO OH
H3COCHN
OH OH

H3COCHN O
O
H3 COCHN
HO
OH O O
O
OH
HO
‘ H3N
OH OH COO-
HOH2C CH C O
H OH

HO
H3COCHN

Fig. (5). Nanoparticles in Ophthalmic Drug Delivery (Reprinted with permission from Barbu et al. Copyright 2006. Royal Society of
Chemistry).
Encapsulated Drug (Doxorubicin)

Biotin-BSA-Gd-DTPA
Biotin-Anti-CD3
(T-cell target)

Fig. (6). Multifunctional Solid PLGA Nanoparticles Tethered to T cell target and MRI Contrast Enhancer(biotin BSA-Gd-DTPA) and
Encapsulating Immunosuppressive Drug (Doxorubicin)(Reprinted with permission from Fahmy et al.Copyright 2007. American Association
for Pharmaceutical Scientists).
4.4. Replacements, Supports and Engineered Tissues roxyapatite [113] based, collagen based or ceramic based
nanoparticles [114].
Polymeric core shell nanocomposite is the most com-
monly used transplant material. These can be polymer/ 4.5. Miscellaneous Application
polymer or polymer/metal, either ways forming core/shell
Nano-nanoparticles can be used for lipid and protein
structures. They are used in dental braces and in joint
detection by modifying their surface with suitable charged or
replacements [111]. Ultra high molecular weight poly-
specific binding moieties. This is a boon because it reduces
ethylene(UHMWPE)/silver [34] is one such material that’s
size of the testing kits and offers high sensitivity [115-118].
used in joint replacement. The salient features that are
They are used in medical dressing for quicker wound
considered in the choice of these materials for joints are healing. These have the property of absorbing fluids and can
abrasion resistance, high impact strength and resistance to
be medicated that can help in consistent wound healing
corrosion. Biomimetic nanoparticles seem to be better
[119]. There are nanoparticle structures that are used by the
materials for joint replacements [112] as they closely
nutraceutical industry. They are expected to deliver nutrients
resemble the biological structure and behave almost simi-
more efficiently than normal drug capsules [120]. They are
larly. But they are a bit expensive and are still at the research
also used to design filter material for better and efficient
stage. Some nanoparticles are being worked on to be used as separation of components. This application is not restricted
artificial conjunctiva [104,105]. Tissue engineering is also
only to the biological industry [99,119,121,122]. Other
looking up to nanoparticles for design of suitable scaffold for
application that’s common to both biological and the
seeding and proliferation of the cells to develop artificial
chemical industry is that of catalytic activity enhancement
tissues. This shows the salient features of nanoparticles that
[121]. Enzymes immobilized on core/shell nanoparticles or
makes it a preferred choice for different purposes with
catalysts encapsulated suitably into nanoparticles have
suitable modification. Materials used commonly are hyd-
40 Recent Patents on Biomedical Engineering, 2008, Vol. 1, No. 1
higher activity than usual [123]. Some find applications a
biosensors [14].
5. FUTURE WORK
The work discussed above brings forth the green aspects
of the new generation “Smart” materials. The dark side that
needs to be considered and modification worked upon hasn’t
been discussed. The prime concern is the retention of these
particles in the body and the harmful effect in the long run.
The other concerns are the result reproducibility in vitro and
in vivo. We have to see if the particles behave similarly in
vitro and in vivo and also if they trigger side reactions in
vivo. Infections caused by the nanoparticles in the case of
transplants and suitable modifications have to be worked
upon. If the particles are conjugated with charged moieties
then the concern is the range of shift in pH for which the
charge is maintained. The change in charge might be toxic
and start adverse reactions or may not produce desired
results. The charge on the particle can also affect the ejection
route from the system hence the biodistribution can vary.
Even for use as biomarkers or as drug carriers it’s essential
to determine the concentration below which these materials
are not cytotoxic.These are the chemical characteristics that
affect toxicity. The physical properties of these materials
also affect toxicity. The size of the particles is a parameter
that has effect not only on the toxicity and retention but also
on the mode of administration. If the particles are too big
they cannot be injected into the system. The physical
properties and the chemical properties can to some extent be
controlled by the synthesis strategy and the modifications
that the synthesized particles are subjected to. And
biocompatibility of the material used is also an important
parameter. Thus, synthesizing particles that are biocom-
patible and are cytotoxic only at very high concentrations is
being aimed at. This makes biomimetic synthesis methods
more preferable and in material selection biopolymers seem
to be promising. Further work on improving core/shell
nanoparticles might help us see, in use, in future, medication
that multi-task: functions of imaging, therapeutics and
specific cell targeting.
The materials discussed above gives an overview of the
options that one can choose from. And the choice is very
much determined by the application of the particles. The
applications decide the type and the size of the particles
which affect particle properties. For imaging applications
heavy metal nanoparticles might offer a good fluorescence
but cytotoxicity is a parameter one needs to consider. The
lanthanide based upconversion particles seems to be a better
option and needs to be worked upon. Similarly instead of
coating the shell with silica some biopolymers have been
tried and we still need to prove that the latter are better when
it comes to biocompatibility than the former. For drug
delivery application it is preferred that the outer shell is a
polymer so that antibodies or targeting agents can be
attached. The basic criteria for the shell are the availability of
functional groups for modification. Functionality of the
particles can be increased by using a core that has
luminescent properties and encapsulating drug between the
core and shell. The core can be quantum dots and the shell
can be a thermo-sensitive or pH-sensitive polymer, thus drug
release can be controlled. As for tissue engineering and
Sounderya and Zhang
replacements, the material used has to mimic their the
biological part they are replacing. For joint replacements
hydroxyapatite base materials seem to hold potential while
for tissue engineering biopolymer based scaffolds can be
developed.
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