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A Nanocage for Nanomedicine: PolyhedralOligomeric Silsesquioxane (POSS)
Hossein Ghanbari, Brian G. Cousins, Alexander M. Seifalian*
Ground-breaking advances in nanomedicine (defined as the application of nanotechnology inmedicine) have proposed novel therapeutics and diagnostics, which can potentially revolu-tionize current medical practice. Polyhedral oligomeric silsesquioxane (POSS) with a distinc-tive nanocage structure consisting of an inner inorganic framework of silicon and oxygenatoms, and an outer shell of organic functional groups is one of the most promisingnanomaterials for medical applications. Enhanced biocompatibility and physicochemical(material bulk and surface) properties have resulted in the development of a wide rangeof nanocomposite POSS copolymers for biomedical applications, such as the development ofbiomedical devices, tissue engineering scaffolds, drug delivery systems, dental applications,and biological sensors. The application of POSS nanocomposites in combination with othernanostructures has also been investigated including silver nanoparticles and quantum dotnanocrystals. Chemical functionalization confers antimicrobial efficacy to POSS, and the use ofpolymer nanocomposites provides a biocompatible surface coating for quantum dot nano-crystals to enhance the efficacy of the materials for different biomedical and biotechnologicalapplications. Interestingly, a family of POSS-containing nanocomposite materials can beengineered either as completely non-biodegradable materials or as biodegradable materialswith tuneable degradation rates required for tissue engineering applications. These highlyversatile POSS derivatives have created new horizonsfor the field of biomaterials research and beyond.Currently, the application of POSS-containing poly-mers in various fields of nanomedicine is under inten-sive investigation with expectedly encouragingoutcomes.
Dr. H. Ghanbari, Dr. B. G. Cousins, Prof. A. M. SeifalianCentre for Nanotechnology and Regenerative Medicine, UCLDivision of Surgery & Interventional Science, University CollegeLondon, London, NW3 2QG, UKE-mail: [email protected]. A. M. SeifalianUniversity College London, Royal Free Hampstead NHS Hospital,London, NW3 2QG, UK
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Introduction
Recent advances in nanotechnology have resulted in the
emergence of advanced novel nanomaterials with
improved properties capable of being used in several
biomedical applications. The application of nanotechnol-
ogy in medicine has led to an emerging interdisciplinary
field called nanomedicine, which can revolutionise current
medical practice. In particular, the development of
advanced diagnostic and therapeutic tools based on
nanotechnology hold great promise in overcoming
library.com DOI: 10.1002/marc.201100126
Hossein Ghanbari completed hismedical degree in 2002 andwas awarded a Ph.D scholarship inmedical nanotechnology in2007. He did his PhD at University College London, Centre for Nanotechnology and Regenerative Medicine and aftergraduation in 2010 has been working as an Assistant Professor in the Department of Medical Nanotechnology, School ofAdvance Technologies in Medicine of Tehran University of Medical Science. His research interests are development ofbiomedical and cardiovascular devices using nanomaterials, application of nanotechnology in regenerative medicine anddevelopment of nanoparticles and nano-structured composite materials for medical application.
Brian G. Cousins joined the groupworking on haemocompatibility and endothelisation of bypass graft materials funded bythe Welcome Trust. He has degrees in Biochemistry and Biophysics studying physical analysis of biological interactions atsurfaces (University of Liverpool, MRes 2001). He completed his Ph.D in Clinical Engineering investigating surfacemodification of biomaterials with nanoparticulate coatings to evaluate cellular behaviour. He is experienced at workingat the interface of interdisciplinary science studying nanomaterial interactions. He is currently at UCL in the Division ofSurgery and Interventional Science in the Royal Free Hampstead NHS Trust Hospital as lecturer in Nanotechnology andBiomaterials.
Alexander Marcus Seifalian is Professor of Nanotechnology and Regenerative Medicine and Director of Centre forNanotechnology & Regenerative Medicine at University College London. He is based within Division of Surgery &Interventional Science. He has completed his education at University of London and University College London MedicalSchool. He is Fellow of the Institute of Nanotechnology (FIoN) and has published over 325 peer-reviewed research papers, 31book chapters and 4 families of patents. During his career, he has led and managed many large projects with multi-disciplinary teams with very successful outcomes in terms of commercialisation and translation to patients, includingdevelopment and commercialisation of a bypass graft for vascular access for haemodialysis; laser activated vascularsealants that have been commercialised for liver and brain surgery, and regeneration of lacrimal duct using nanomaterialsand stem cells. His current projects develop cardiovascular implants using nanomaterials and stem cells technology, organsusing tissue engineering, nanoparticles for detection and treatment of cancer, and he is also working on nerveregeneration and development of skin. He has been awarded the top prize in the field of development of nanomaterialsand technologies in the development of cardiovascular implants in 2007 by Medical Future Innovation and in 2009received a Business Innovation Award from UK Trade & Investment (UKTI) in the Life Sciences and Healthcare category.His current grant sum is £3.2 million.
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unsolved problems of traditional medicine. Several nano-
structured materials have been explored for potential use
in medicine, ranging from the application of nanoparticles
or nanostructures in cell labelling,[1] to diagnostic and
imaging tools[2] for advanced therapeutic modalities such
as precise drug delivery systems using nanocarriers for
cancer treatment.[3,4] Since synthetic nanomaterials are
inherently small, with at least one dimension in the
1–100nm range, they can widely interact in the physio-
logical environment by crossing the biological membrane
barrier.[5] This is of particular advantage in developing
novel diagnostics and therapeutics based on nanomater-
ials.
The properties of the materials change considerably
when the size is significantly smaller in comparison to the
larger micrometer-scale components of the samematerial.
Nanomaterials generally exhibit improved physical, che-
mical, and mechanical properties compared to their
conventional counterparts. The superior properties of
nanomaterials offer potential applications in a wide range
of scientific disciplines. They can be used directly or
indirectly by being incorporated into polymeric systems
to create nanocomposite materials. Principally, composite
materials are combinations of at least two constituents
with significantly improved physicochemical properties.
Matrix (host) and reinforcement (guest) phase components
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are themain reactive constituents behind the vastmajority
of composite materials. The interactions between mono-
mers that form the macromolecular components and their
final structures vary according to the type of starting
materials and fabrication techniques used. When at least
one of the components is of nanometer-scale dimensions,
the resulting composite is considered a nanocomposite
material.[6] In nanocomposite polymers, the synthesis
method and the nature of the nanofiller or monomer
(method of nanoreinforcement) determines the type of
micro- andmacromolecular scale interactions between the
polymeric matrix to regulate the behaviour of the
nanocomposite’s physical and structural properties.[7–9]
Among the most commonly studied nanofillers or
monomers for developing composite materials is the
silsesquioxane family. The chemical structure of the
silsesquioxane family is defined as RnSinO1.5n, which forms
structures consisting of an inorganic framework of silicon
and oxygen atoms, surrounded by organic side chains (R
group).[8,9] The R group can represent a range of functional
species such as hydrogen, alkyl, alkene, aryl, and arylene
moieties. Based on their molecular architecture, silses-
quioxanes can be classified into two main categories. The
first category includes non-caged silsesquioxanes that form
ladder, random, and partial-caged molecular struc-
tures.[10,11] Suchsilsesquioxaneswith ladder-like structures
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H. Ghanbari, B. G. Cousins, A. M. Seifalian
inpolymeric systemsshowenhanced insulatingproperties,
gas permeability, and play host to a range of applications
from surface coatings and gas separation membranes to
binding agents for carcinostatic drugs.[8,10–12] The second
category includes the caged silsesquioxanes.[8,9]
Conventionally, caged molecular structures such as
polyhedral oligomeric silsesquioxanes (POSS)[13] are one
group of the silsesquioxane family that posses a regular
three-dimensional (3D) shape formed by a few units each
containing silsesquioxane.[9] This structure consists of an
inner inorganic framework of silicon atoms (n¼ 8) linked
with oxygen atoms (n¼ 12), and an outer shell of organic
groups (n¼ 8) that merge together to form a 3D cubic
nanocaged structure (Figure 1). Hence, each silicon atom is
bonded to threeoxygenatomsbysiloxanebonds (Si�O�Si),
and one carbon silicon bond (Si�C) that may be inert or
reactive, thus rendering the nanostructures compatible
with polymeric and biological systems. These are highly
Figure 1. Schematic structure of A) trans-cyclohexane chlorohydrin isobatoms, surrounded by organic side chain groups (R¼�CH2CH3CH3), anapplications.
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symmetrical molecules with a nanoscopic feature size of
approximately 1.5 nm in diameter (including the R side
chain groups), and can be considered as the smallest of
achievable silsesquioxane particles.[8,14] POSS differs in
structure and chemistry to silica (SiO2). Inorganic SiO2, both
colloidal and amorphous, have a defined 3D spherical
morphology composed of cross-linked Si�O�Si with sur-
face silanol (Si�OH) groups (instead of Si�C), and range in
size from 5 to 100nm in diameter (leading to micrometer
scaledimensions for amorphous SiO2).When thenumber of
silicon atoms increase within the POSS structure (were
n¼ 10 or 12) the nanocages are somewhat larger than
1.5 nm, but usually< 5nm in diameter. Despite their small
size it is conceivable that aggregation of POSS occurs
naturally in polymeric systems (when acting as a
nanofiller) forming dispersions of nanoparticulate materi-
als ranging from 10–100nm in diameter.[8] For example,
studies have shown that gas phase cross-sectional analysis
utyl-POSS consisting of an inner inorganic core of silicon and oxygend B) POSS-PCUnanocomposite polymers developed for cardiovascular
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of POSS (RnSinO1.5n) with increasing cage size (n¼ 6, 8, 10,
12, and 14) revealed structures ranging from 14 to 26nm in
diameter with similar dimensions to amorphous and
colloidal SiO2.[15,16]
Theorganic side chaingroup (R) on theouter shell of POSS
has a potentially unlimited supply of organofunctional
inert or reactive groups derived from alkyl, olefin, alcohol,
ester, anhydride, acid, amine, imide, epoxide, thiol,
sulfonate, fluoroalkyl, silanol, and siloxide functional-
ities.[9] Indeed, researchers have shown that reactive POSS
monomers can be incorporated as nanomolecular scale
building blocks[17] forming hybrid inorganic–organic copo-
lymers.[18,19] In this way, copolymerization of POSS
monomers results in covalent modification driven by
self-assembly processes, e.g., hydrogen bonding, electro-
static, andp–p stacking interactions (in the caseof aromatic
functional groups), which leads to aggregation, crystal-
lization, and cross-linking of POSS nanocages within the
hard segments of the polymeric matrix and results in
enhanced thermal, mechanical, and physical proper-
ties.[9,18,19] Thesize rangeofPOSSaggregatesandcrystalline
segments embedded within the polymeric matrix range
from 10 to 20nm in diameter.[16] Physical and thermal
properties are improved by the incorporation of POSS with
low dielectric constants (K),[20] increased glass-transition
temperatures (Tgs),[20–22] a low coefficient of thermal
expansion, thermal stability, and heat evolution.[14,23]
Improvements in the mechanical properties show
increased tensile strength,[21,22,24] viscosity,[14,24,25] and
enhanced viscoelastic properties.[19,26,27] Further improve-
mentshavealsobeen reported suchas oxidation resistance,
reduced flammability, oxygen permeability, and reduced
inflammatory reactions, which highlight the key advan-
tages of using such materials for biological applica-
tions.[21,22,24,28] The incorporation of POSS influences the
surface properties such as surface chemistry (wettability),
energy, and topography. Efficient surface coverage and
stability under a variety of environmental and physiolo-
gical conditions are part of the POSS derivatives’ unique
features thatmake them attractive as surfacemodification
agents.[29] Incorporating POSS structures by non-covalent
modification of nanoparticles yields a variety of 3D
materials composed of palladium, magnetic (iron, nickel
and cobalt), and gold nanostructures.[30–35] The unique
characteristics of POSS nanomaterials offers a diverse
application potential in a wide range of areas from
biomedical to biotechnological fields, and are currently
under intensive investigation.
Application of POSS in Nanomedicine
The unique structures and superior surface properties of
POSS allow them to be used in the structure of different
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polymers and copolymers developed for biomedical appli-
cations. In particular, owing to their biocompatibility and
ability to incorporate additional polymers, POSS nano-
structures have been shown to offer high potential in
several biomedical applications such as drug delivery
systems,[36,37] dental composites,[38] biosensors,[39] biome-
dical devices,[40–42] and tissue engineering products.[43,44]
Because of their relatively inert nature and reduced
inflammatory response, the molecular structures of POSS
consisting of Si�O�Si and Si�C groups has similar
chemistry to silicone elastomers (poly(dimethylsiloxane),
PDMS), which has been a preferable biomaterial since the
1960s when it was introduced in breast implantation.[45]
Biocompatibility is one of the key features of POSS
nanomaterials resulting from the increased surface energy
in the foci of silicon-rich areas. Non-toxicity and cytocom-
patibility are other fundamental features of POSS making
them suitable for biomedical applications.[46–48] For exam-
ple, a recent study evaluated the in vivo degradation of
polyester polyurethanes over a 24week period using cross-
linkedPOSSas thehard crystalline segment.[49] Itwas found
that no acute chronic inflammatory response was evident
over a three week time period. Such studies concluded that
polymeric thin films and biodegradable formswere indeed
biocompatible, and did not initiate a chronic inflammatory
response often characteristic of cytotoxic non-compatible
biomaterials.[49] Hence, polymeric POSS-based nanocom-
posites have been largely studied by biomaterial scientists
with the aim of utilizing and understanding their unique
physical and chemical properties, and how these phenom-
enaare translated to influence thebiological responseat the
tissue–implant interface for biomedical and tissue engi-
neering applications.
POSS Nanocomposites in Cardiovascular Implants
Haemocompatibility is an essential requirement in cardi-
ovascular applications of biomaterials. Since cardiovascu-
lar implants are directly in contactwith blood, thematerial
used in their structure and the device itself should not
induce any thrombosis and damage to red blood cells
(haemolysis). To meet the essential requirements for these
applications, we have developed nanocomposite materials
by copolymerization of POSS monomers with poly(carbo-
nateurea)urethane (POSS-PCU) to formcovalentlymodified
and cross-linked nanostructureswithin the hard segments,
and form pendant chain groups.[10,50–53] Studies on its
cytocompatibility, anti-thrombogenicity, and biostability
have shown that this nanocomposite polymer has unique
characteristics for applications at the blood–biomaterial
interface.[52] This nanocomposite polymer can be biofunc-
tionalized by anchoring peptides and growth factors
through surfacemodification in order to attract endothelial
progenitor cells (EPCs) from the circulatory blood, and
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Figure 2. Schematic images showing biofunctionalization of the surface of POSS-PCU to create smart scaffolds for in vivo tissue engineering.A) The surface can be modified by grafting specific bio-active peptide motifs or other ligands or receptors into POSS-PCU. B) Thebiofuctionalized surface can target several biological processes to promote in situ endothelialization by promoting themobilization of EPCsfrom the bonemarrow, encouraging cell-specific (circulating EC, EPC, and stem cells) homing towards the vascular graft, providing adhesionmotifs (of a predetermined spatial concentration), and directing the behaviour of the cells to rapidly form a mature fully functioningendothelium with self-repair capability (C).
Figure 3. Development of cardiovascular devices using a POSS-PCU nanocompositepolymer. Digital images are presented in (A) illustrating an example of a small diameterbypass graft modified with 2% POSS-PCU. The longest portion of the graft (centre) is5 cm in length with an internal diameter of 5mm, and a porous wall structure approx.0.85–0.9mm in thickness. B) A preclinical assessment of the positioning and implan-tation of a small diameter bypass graft composed of 2% POSS-PCU sutured in to thecarotid artery of an ovine model.
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H. Ghanbari, B. G. Cousins, A. M. Seifalian
become endothelialized to enhance the bio- and haemo-
compatibility of cardiovascular devices made with this
material (Figure 2). Recently, we have developed small
diameter coronary artery bypass grafts composed of POSS-
PCU, which are undergoing preclinical assessments in vivo
in a large animal model (Figure 3). Heart valves,[41]
percutaneous heart valve prostheses, stent grafts, and
nanocomposite-coated coronary stents using POSS-PCU are
currently under investigation. Novel synthetic leaflet heart
valves based on the POSS-PCU nanocomposite have
recently been developed and are currently undergoing
further evaluation. These valves can potentially combine
the advantage of improved mechanical strength of
bioprosthetic valves, and eliminate their apparent dis-
advantages. In addition, using a electro-hydrodynamic
spraying approach, we have established the application of
POSS-PCU for the coating of metallic stents, and demon-
strated that polymeric nanocomposites have the potential
to be used in the development of anewgeneration of stents
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with improved properties, especially
with small diameter stents for use in
the coronary artery.[54] More recently,
biodegradable drug-eluting stent coat-
ings have been developed using a ther-
moplastic polyurethane (TPU) with POSS
hard segments (POSS-TPU) and soft seg-
ments composed of poly(L-lactide)/capro-
lactone copolymers (P(DLLA-co-CL) with
covalent attachment of poly(ethylene
glycol) (PEG).[55] The soft segments were
designed to modulate the drug release of
paclitaxel, a knownmitotic inhibitor and
anti-proliferative agent used to treat
patients with cancers, and to prevent in
situ restenosis. The results demonstrate
that biodegradable POSS-TPU loaded
with paclitaxel allows drug release that
can be controlled by variation in polymer Tg with
degradation rates tunable by coating thickness under
physiological conditions.[55] Furthermore, recent studies in
thedesignofdegradablepolymers suggest overall improve-
ments in the miscibility of paclitaxel over a range of
concentrations, which can be fine tuned by specific
interactions of degradable POSS-TPUs.[56]
POSS-PCU has been characterized and assessed for
biomedical applications in general, and for cardiovascular
applications in particular, and the results of such studies
reveal that POSS-PCU nanocomposites contain enhanced
physical and chemical characteristics which create a
technology platform for biomedical applications. This
polymer is currently being used in the design, fabrication,
and manufacture of medical devices, including microvas-
cular beds for organ tissue (including liver), muscle,
cartilage, and breast implants,[50] materials for coating
quantum dot nanocrystals for cancer detection, improved
contrast agents for magnetic resonance imaging (MRI),
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small-diameter artificial naso-lacrimal duct conduits, and
several further applications related to tissue engineering
using modern surgical techniques.
POSS Nanocomposites as Coating Materials forQuantum Dot Nanocrystals
Quantum dots (QD)s are luminescent nanocrystals that are
undergoing intensivedevelopments to create anewclass of
contrast agents for MRI.[57] As the next generation of
fluorescent probes, QDs owe their novelty to their large
absorption, narrowanddiscretemulticolour light emission,
bright photoluminescence, high photo-stability, and nano-
meter-scale dimensions ranging from less than 1.5 nm
to 50nm in diameter. Indicating a range of QDs of around
1-50 nm in diameter. In the next few years, developments
of such nanoparticles will bring improved and unique
insights into a variety of biomedical imaging applica-
tions.[58] QDs are already revolutionizing the processes of
tagging macromolecules, proteins, antibodies, and cells,
and the detection of specific cancers such that they may
guide surgical procedures in vivo.[59,60]
As new approaches in medical engineering of QDs
for biological applications are being developed, there is
concern regardingtheirdegradationrates invivo, especially
their oxidation.[61] To avoid premature degradation,
enhance biocompatibility, and to reduce their potential
toxicity, coating QDs with a biocompatible and biostable
polymer has been proposed. POSS-PCU is a potential
material for coating QDs where nanosized POSS is
covalently attached to PCU, and the nanocomposite used
as a surface coating to enhance the mechanical properties
and impart greater resistance to biodegradation, as
discussed previously. Such POSS-PCU coatings have been
studied in detail, and have been shown to be non-toxic,[48]
biocompatible,[52] and biologically stable.[62] POSS-PCU has
also been shown to possess hydrophilic groups in experi-
ments exploring its putative applications in various
biomedical devices. A recent study characterized the
biocompatibility of QDs encapsulated with POSS-PCU
nanocomposites. In this study, the in vitro cytocompat-
ibility and potential cytotoxic effects were investigated
usinghumanumbilicalveinendothelial cells (HUVECs). The
maximum tissue depth at which these nanocomposite-
coatedQDs (NCCQDs) could bedetectedwas also addressed.
NCCQDs were of a narrow size distribution with a mean
hydrodynamic diameter of 10.5 nm, high photo-stability,
excellent monodispersity, and a large absorption spectrum
with a narrow and discrete emission band at 790nm.
NCCQDs were non-cytotoxic to HUVECs in culture: viable
cells were shown to be present after 14 d when the media
was exposed to NCCQDs. Exposing cells to NCCQD-treated
cell culturemediumresulted innoapparentdamage to cells
at concentrations of 2.25� 10�2 nM. NCCQDswere detected
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atamaximumtissuedepthof10mminsolid tissuesamples
using a near infrared camera (Figure 4). POSS-PCU surface
coatings provide an opportunity to modify the QD surface
and alleviate any potential toxic effects of cadmium
telluride (CdTe) nanocrystals to endothelial cells (ECs).
Recent advances in microscopy have shown that two-
photon excited fluorescence (TPEF) can detect POSS
conjugated with oligoelectrolytes (COE) for imaging the
cell nucleus. The 3D hybrid nanodots (COE-POSS) have been
visualized and detected in breast cancer cells (MCF-7), and
were more effective at highlighting and distinguishing
between the nucleoli from other compartments of the
nucleus than one-photon excited fluorescence (OPEF). COE-
POSS was also found to be superior to commercially
available SYBR green (SG) dyes, and may have great
potential in areas such as clinical diagnostics.[63]
Antibacterial Agents Using POSS
Anarrayofquaternaryammoniumcompounds canbeused
to functionalize POSS (Q-POSS) for antimicrobial applica-
tions. In a recent study, Majumdar and co-workers
investigated the antimicrobial activity of Q-POSS coatings
towards Escherichia coli, Staphylococcus aureus, and the
opportunistic fungal pathogen, Candida albicans using a
standard Agar plating method (Figure 5). The results
showed that the composition of Q-POSS and the polysilox-
ane matrix affected the antimicrobial properties. Several
compositionswere identified that inhibited growth in all of
the microorganisms studied on the coated surfaces.
Although their potential benefits warrant further investi-
gation as immobilized quaternary compounds, such
materials are known to cause inflammatory and anaphy-
lactic reactions in general surgery.[64] Recent studies have
also revealed that hydrogels synthesized from PEG and
POSS-containing polyurethanes, electrospun into nanofi-
bers (150nmindiameter)withorwithout silvernitrate, can
beused to inhibit biofilm formationof E.Coli strains.[9] Such
materials hold great promise in the development of novel
wound dressings for localized wound healing applications.
Silver nanoparticles that range from 1 to 100nm in
diameter are attracting interest as antimicrobial agents for
applications in modern medicine. Recent studies suggest
that Ag nanoparticles have potent anti-inflammatory
properties[65,66] and improved wound healing capabil-
ities.[67] The antibacterial properties of Ag are widely
known, andwell established by their current use aswound
dressings, and in topical ointments for treating burn
patients.[68] The use of Ag in the structure of synthetic
polymeric materials can potentially confer antibacterial
bulkandsurfacepropertiesofbiomaterials. It iswell known
that implantable devices are at greater risk in the
development of hospital-acquired infections during surgi-
cal intervention. Modification of the materials with Ag
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Figure 4. Transmission electron microscopy (TEM) image ofmeasurements of CdTe nanocrystals coated with NCCQD (A).In (B) QDs of various sizes were injected at various depths intoa chicken leg, as a simple model tissue to locate their presenceunder excitation with IR. Fluorescent imaging of MCF-7 cells withOPEF microscopy in (C) and (D) show OPEF/transmission over-lapped images stained with 1mM of COE-POSS. TPEF images ofMCF-7 cells incubated with 1mM COE-POSS (E) or SG (F) for 2 hincubation period. (Images C�F were adapted from ref.[63]).
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nanoparticles can possibly eliminate nosocomial infection
rates in devices that incorporate degradable polymeric
materials (described previously in the development of drug
eluting stent coatings). Because of the understandable
controversy surrounding the toxicity of Ag exposed in
previous studies, research into Ag coatings for heart valves
and other fully implanted cardiovascular applications is
understandably tentative. Currently we are investigating
the antibacterial, mechanical, and haemodynamic proper-
ties of Agnanoparticles impregnatedwith POSS-PCU to test
the efficacy of thesematerials.[69] Preliminary results show
effective kill rates with a 99.9% reduction in total viable
counts using E. coli and S. aureus (unpublished data).
Therefore, Ag modified with POSS within the polymeric
matrix may be a promising development, and can be used
for implantable devices, surface coatings, polymeric tubing
such as catheters, and in particular implants with a higher
risk of infection such as the naso-lacrimal duct during
soft tissue repair and reconstructive surgery. The
cytocompatibility and anti-inflammatory properties of
Ag modified with POSS copolymers are currently under
investigation.
Development of POSS-Containing Breast Implants
Silicone implants are used extensively for a range of
augmentation procedures worldwide, especially in breast
implants. The procedure was first introduced during the
1960s, and used what was originally thought to be a
relatively inert biomaterial with minimal complications
and inflammation rates. However, long-term studies
suggest that silicone delays wound healing,[70] and
is responsible for capsular contracture and repetitive
movement causes pseudo-inflammation because of the
release of microparticles (forming silicone wear debris).[71]
POSS derivatives can potentially be an alternative option
for silicone in breast implant products. In a recent in vivo
study[50] it was shown that POSS-containing polymeric
materials revealed no sign of significant inflammation and
material degradation compared with siloxane controls.
Hence, it was concluded that these nanocomposites
improved the interfacial surface properties and biological
stability compared with conventional silicone materials,
which significantly reduced the risks associated with
augmentation procedures.
POSS Nanocomposites in Tissue Engineering
Tissue engineering is a rapidly emerging field, combining
various aspects of medicine, cell and molecular biology,
materials science, and engineering to regenerate diseased
andmalformed tissues and improve organ function.[26] The
3D scaffold materials in tissue engineering are categorized
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Figure 5. Three different antimicrobial responses to Q-POSS. For some coatings, no microorganism growth was observed in a zonesurrounding the coated specimen (zone of inhibition (þ,þ ). In addition, coatings were identified that showed nomicroorganism growth onthe coated surface, but no zone of inhibition (þ,–). Coatings that showed no microorganism growth inhibition or a zone of inhibition weredesignated (–,–) (Image adapted from ref.[9]).
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as natural or synthetic materials. The advantage of
synthetic scaffolds over natural biological materials is that
their production techniques are known, their structure is
controllable on both macro- and microscopic scales, and
they are biodegradable over time with controlled degrada-
tion rates. In principle, polymer scaffolds are desired to be
biocompatible with various mechanical properties, which
sustain hydrodynamic shear stress at a specific site of
application.[27,72,73] They should possess good cell adher-
ence, and subsequent proliferation and differentiation.
Moreover, cytotoxicity of the polymer scaffolds is another
crucial factor affecting cell viability either by direct contact,
or by releasedproducts throughdegradation, and should be
taken into consideration during their design.[74]
The physical characteristics of porosity such as pore
structure, volume, and size are responsible for the regula-
tion of cell function. Highly porous scaffolds offer a
significant surface area for cell attachment and inclusion.
The key factor responsible for successful cell adhesion,
proliferation, and differentiation is pore interconnectivity.
Good pore interconnectivity provides a sustainable envir-
onment for uniform cell distribution within the scaffold,
and plays an essential role in regulating the diffusion of
nutrients and recycling of waste products.[27,72,73]
The most common POSS-containing polymer to date for
biomedical and tissue engineering applications is a non-
biodegradable nanocomposite based on POSS-PCU. Despite
the traditional view, which describes an ideal polymeric
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scaffold for tissue engineering applications to be biode-
gradable and able to reduce the potential of immunogenic
reactions, recent research implies that anon-biodegradable
polymer may be equally as effective in terms of providing
mechanical strength and stability. The presence of POSS on
the surface of the polymer induces specific micro- and
nanometer-scale topography through cross-linking, which
favours cell attachment and proliferation in certain cell
types (Figure 6).
The incorporation of POSS into polycaprolactone (PCL)
andPCUhas resulted in thedevelopmentofabiodegradable
polymer that preserves its mechanical properties as it
undergoes oxidation, hydrolysis, and degradation in the
biological environment. This has been trademarked at
University College London (UCL) (UCL-NanoBio) and con-
sists of 80% (w/w) polyhexanolactone and 20% (w/w) PCU.
The nanomaterial provides a ‘shielding effect’ on the soft
segments of the nanocomposite polymer.[75]
Gupta et al.[26] studied non-biodegradable POSS-PCU and
biodegradable POSS-PCL-PCU which had been subjected to
an electro-hydrodynamic printing technique in the pre-
paration of tissue engineering scaffolds for use in the small
intestine and liver, and for cartilage repair. The results
demonstrate that the technique can offer significant
benefits in the development of artificial organs.
In a further study, the cell compatibility of the UCL-
NanoBio polymeric system was investigated in vitro. The
direct effect of the polymers with peripheral blood mono-
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Figure 6. A) Atomic force microscopy (AFM) image of POSS-PCU showing micro- andnanotopography induced by agglomeration of POSS nanocages on the surface (scanarea: 100� 100mm2). In (B) a SEM image highlights EPCs cultured on POSS-PCU showingthe presence of colonies (arrows) attached to the surface after 7 d of culture. Thissupports the view of in situ endothelialization potential of POSS-PCU nanocompositesfor cardiovascular applications.
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H. Ghanbari, B. G. Cousins, A. M. Seifalian
nuclear cells (PBMCs) and human stem cells was studied by
seeding cells on to circular polymeric disks prepared by
electro-hydrodynamic jetting. To assess effects of the
polymer, different polymer concentrations ranging from
1 to 100 mg �mL�1 were added to culture media and left to
incubateonacell orbital shaker for10d.Theprecipitatewas
removedandthemediaextractswereused for testing incell
culture. Cell viability and growth at 48 and 96h were
analysed using Alamar Blue and lactate dehydrogenase
(LDH) assays. Cell morphology was studied using scanning
electronmicroscopy (SEM). Cellswere shown to adhere and
spread on the polymer surface with metabolic activity
comparable to that found on tissue culture polystyrene
(TCPS). Cell viability on the polymer scaffolds formed using
both electro-spraying and electro-spinning was compar-
able with cells seeded on TCPS, but infiltration into the
scaffold was much more evident on the electro-spun
scaffolds. Itwas foundthat thenanocompositematerial can
support cell adhesion, growth, and viability of human stem
cells, and that the scaffolds fabricated by electro-hydro-
dynamic jetting methods have potential for tissue engi-
neering applications in the near future.[44] The application
of this biodegradable nanocomposite was explored for the
development of scaffolds for the small intestine. Scaffolds
of the POSS-PCL-PCU nanocomposite produced a range of
porous structures with surface porosity ranging from 40 to
80% and a mean pore size of 150 to 250mm. The polymeric
scaffolds were seeded with rat intestinal epithelial cells
over 21 d. The results demonstrate that such scaffold
materials support intestinal epithelial cell proliferationand
growth with improved physical and chemical properties
that resulted in sustained viability and proliferation.[43]
As mentioned earlier, chemical compositions can have a
significant influence on themechanical properties of tissue
engineering scaffoldsandontheadhesionandproliferation
of cells within the scaffold structure.[76,77] Therefore,
various studies have been implemented to manipulate
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the chemical composition of synthetic
biomaterials for improved cellular and
tissue responses in tissue engineering
applications.
More recently, the effect of POSS on
polyester urethane (PEU) was analysed
for the purpose of tissue engineering
applications using different analytical
measurements (e.g., microscopic analy-
sis, NMR spectroscopy, X-ray diffraction
(XRD), differential scanning calorimetry
(DSC), thermogravimetry, and dynamic
mechanicalanalysis).[78,79] Itwasdemon-
strated that the incorporation of POSS
(6%w/w) into themacromolecular struc-
ture of PEU by in situ homogeneous
solution polymerisation resulted in a
new hybrid POSS-PEU nanocomposite with remarkable
improvement in thermal and hydrolytic stability, stiffness,
strength, and degradation resistance compared to PEU
controls.[79,80] Further investigations of the surface and
structuralproperties, andcell compatibilityof thePOSS-PEU
nanocompositeusingmurineembryonic stemcells (mESCs)
revealed that although the incorporation of POSS did not
have a direct influence on cell adhesion, viability,
proliferation, and differentiation, it significantly changed
the surface architecture of PEU into a 3D matrix with
regular pore features and could potentially enhance the
biocompatibility of the nanocomposite polymer. The SEM
image analysis illustrated that there were approximately
950 randomlydistributedporespermm2within thematrix,
which equates to approximately 7.6% of the total matrix
surface areawith ameanpore diameter size ranging from1
to 15mm in diameter.[78] Although these structures were
randomly distributed, and the poreswere not large enough
for cell infiltration, the overall matrix appeared to be
uniform with interconnected grooves, and they supported
the access of cells to nutrients and growth factors, and
provided effective nutrient/waste exchange. Under cell
culture conditions the growth rate of mESCs was similar to
that seen in gelatin, exhibiting undifferentiated morphol-
ogywith the expression of pluripotencymarkers. However,
after cell stimulation for differentiation, themorphology of
the mESCs changed dramatically, and the differentiated
cells formed a continuous cell monolayer, which was
embedded within the polymer matrix.[78,79] In summary,
these studies suggest that incorporation of POSS into the
polymer provides a non-toxic nanocomposite with the
potential of fabricating 3D scaffolds aswell as a thinmatrix
with the desired porosity, mechanical strength, and
biodegradability by precise and tuneable reaction proce-
dures.[79,80] In addition, it provides a conducive environ-
ment for cell–cell or cell–matrix interactions, which are
essential for newly formed tissue formation, andhold great
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potential in mESC-based soft tissue engineering applica-
tions.[78]
Drug Delivery Systems
In general, the systemic administration of drugs is
associatedwith some clinical side effects. The aimof newly
proposed drug delivery systems is to carry the intended
drug(s) directly to the site requiring therapeutic interven-
tion. The basic scientific concepts surrounding the use of
nanotechnology-based drug delivery systems closely cor-
relate with the modulation of the pharmacokinetics of
incorporated molecules. With this intimate co-association,
the fundamental properties that govern drug absorption,
distribution, and elimination out of the human body are
determinedby thephysicochemical properties, particularly
by surface exposed functional groups that influence their
surface charge and size.[81] For instance, currently devel-
oped silicone hydrogels can be utilized as a matrix for
transdermal drug delivery,[82] while silicone microspheres
have been developed for pH-controlled drug delivery in the
gastrointestinal tract.[83] Nanocomposites are also being
considered for use in drug delivery systems. Biodegrada-
tion, thermodynamic stability, and biocompatibility, along
with improved surface features are all desired character-
istics that allow the nanocomposites to be considered as
ideal nanocarrierswithahighdistributionpotentialwithin
biological systems. The application of POSS nanomaterials
in drug delivery systems has potential advantages, such as
their being easily transferred by transmembrane and
vascular pores, owing to their small size and high charge
density, which increases the likelihood of cell and tissue
uptake (Figure 7).[36]
In order to assess the efficacy of silsesquioxane
nanocomposites to be used as drug delivery vehicles,
McCursker et al.[36] labelled octaammonium-POSS with a
fluorescent marker (boron-dipyrromethene, BODIPY) by
neutralization of ammonium on the POSS subunits with
triethylamine and substitution with a succinimidyl ester
derivative. BODIPY is a commonly used fluorescent marker
of the cell membrane, which can be readily conjugated to
various other systems to track cellular migration patterns
in vitro. In this study, it was found that the unique
chemistry of POSSwas the key element in the dispersion of
BODIPY conjugates (POSS-BODIPY) in the cytoplasm when
compared with BODIPY alone. Moreover, the conjugate did
not influence the cellular morphology in COS-1 cells. Cell
viabilityassaysproved that thecellswithconjugatehadthe
same activity level as the controls, indicating that POSS
represented low levels of toxicity. Furthermore, dispersion
in the cytoplasm demonstrated that the POSS-BODIPY
conjugate entered into the cells by passive diffusion, not by
endocytosis. The results demonstrated that specific locali-
sation of the conjugate could be achieved within the cell,
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Macromol. Rapid Commun.
� 2011 WILEY-VCH Verlag Gmb
and observations showed that POSS could be used as a
potential drug system by direct conjugation with func-
tional drug moieties that are insoluble in aqueous systems
or that exhibit lower cellular uptake (Figure 7).[36]
More recently Tanaka et al. demonstrated an enhanced
entrapment ability of dendrimers by incorporation of a
POSS central core. Their results showed that the POSS-core
dendrimer can entrap a larger amount of guest molecules
without loss of affinity, and consequently, the water
solubility of the entrapped guest molecules can be
increased. In addition, they demonstrated that a fluor-
ophore entrapped in the POSS-core dendrimer was pre-
vented from undergoing fluorescence photo-bleaching.[37]
Not only do the chemical and physical properties of the
nanosystems, as determinant factors in drug distribution
and kinetics in the biological environment, need to be
optimized, but optimization of manufacturing techniques
for mass production for commercialisation and clinical
translation should be investigated further.[84] Simplifica-
tion of the manufacturing techniques, and optimisation of
targeted drug delivery systems by self-assembly of pre-
functionalised materials, can facilitate high volume man-
ufacturing processes.[85,86] The self assembly process leads
to the construction of a vesicle shell, which contains the
active drug molecules in the centre. These shells are
expected to have strong characteristics in order to prevent
any drug leakage and to avoid immune system recognition
by impeding protein adhesion.[84] Because of their strong
framework and degradation resistance, which results from
intermolecular forces between constituent molecules and
their nearest neighbours, POSS molecules can be used as
templates for the production of drug delivery core–
shells.[36] More recently, a self-assembled spherical amphi-
philic nanoparticle composed of a POSS hydrophobic core
and a poly(vinyl alcohol) (PVA) hydrophilic outer shell has
been studied.[87] In vitro tests have shown that these
nanoparticles areable to releasemodel drugs ina controlled
manner. POSS incorporation also improved the thermal
stability and hydrophilicity of PVA making it a
potential carrier for peptides, drugs, and DNA.[88,89] In
addition, owing to its size and unique nanostructure this
drug delivery system is capable of travelling within the
body and carrying the drug to target regions within the
tissues.[87,90]
In a further recent study, a new nano-drug delivery
system has been proposed based on poly(L-glutamic acid)
dendrimerswith POSS composed of a central core (Figure 7).
By incorporating pH-sensitive functional groups by hydra-
zine bonds and a targeting moiety, the cellular internaliza-
tion and anti-tumour potential of the OAS-G3-Glu den-
drimer conjugated with doxorubicin was assessed in
vitro.[91] In this study the release of doxorubicin at different
rates and pH was investigated and the cellular uptake of
conjugated antibodies using biotin was also analysed. The
2011, 32, 1032–1046
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Figure 7. Fluorescence confocalmicroscopy imageswith POSS-BODIPY show efficient uptake in the cytosol (A). B) Controlmicroscopy imageswith amine-terminated BODIPY show no cellular uptake of the dye in the absence of POSS (image adapted from ref.[36]). In (C) a novel nano-drug delivery and bioresponsive system is presented based on poly(L-glutamic acid) dendrimers with POSS composed of a nanocubic core(image adapted from ref.[91]). In (D) a schematic illustration of therapeutic targeted drug delivery systems based on POSS nanoparticles arehighlighted as follows: I) POSS incorporated into the drug delivery system, II) migration of the drug delivery system through capillary wallstowards the targeted primary tumour cell site, III) attachment of the nano-drug to the malignant cells by specific receptors, and IV)therapeutic effects of the drug and significant reduction and elimination of the malignant cell population.
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H. Ghanbari, B. G. Cousins, A. M. Seifalian
results demonstrated that the spherical morphology,
compact structure, and functional groups around the
periphery of the core–shell enabled this nanosystem to
be a suitable candidate for drug delivery applications.[91]
In line with established pharmacological studies, it
appears that attention is growing towards the application
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� 2011 WILEY-VCH Verlag Gmb
of nanoparticles for chemotherapy, drug delivery, and
imaging. For example, in tumour diagnostics, the physi-
cochemical features of the nanoparticles such as particle
size, surface coating, charge, and stability allow the
qualitative or quantitative in vitro detection of tumour
cells at the site of interest. In this case, nanoparticles can
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A Nanocage for Nanomedicine . . .
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act either by direct or indirect mechanisms. Taking
advantage of tumour vasculature hypermeability can
give the nanomaterials the flexibility of direct targeting of
primary tumours in the tissues. However, in an indirect
way these particles can target the tissue or cells near the
tumour and act as a drug reservoir to prevent proliferation
and migration of adjacent neoplastic cells. A controlled
drug delivery system at the site of interest, cell inter-
nalisation, efficient drug protection, and prevention from
premature inactivation during transportation seems to be
achievable if designed appropriately by utilising the
physicochemical properties of the nanoparticles by way
of design, e.g., incorporating chemical functionality and
specificity into the 3D structure.[92]
Dental Nanocomposites
Dental composites and methacrylate-based polymeric
systems have been used extensively for hard and soft
lining materials (usually alongside metallic and ceramic
materials). Resin-based acrylic polymers, inorganic glass,
or ceramic fillers are commonly used materials as filling
and restorative composites in dentistry.[93] The acrylate
resinmatrix is usually cured (hardened) byphoto-initiated
free radical polymerisation.[38] Despite increased efforts to
improve the overall mechanical properties of dental
materials, there is still considerable research efforts in
addressing their physicochemical characteristics. For
example, polymerisation shrinkage, wear resistance,
biocompatibility, lack of strength, toxicity of monomers,
and modulus of elasticity are all key research themes. In
addition, inflammation as well as hypersensitivity reac-
tions to dental materials, although rare, have been
reported.[47,94]Much effort is nowbeingmade to overcome
potential drawbacks in specific applications. More
recently POSS-containing nanocomposite materials are
being considered as potential candidates to improve
material and surface properties. The potential for POSS
inclusion in the modification of dental materials was first
proposed by Sellinger and Laine in 1996.[95] The small size
of POSS structures when compared with other nanofillers
(10–100 nm) is a unique characteristic, as well as having a
wide range of chemical functionality to incorporate
reactive chemical groups. Moreover, an increased Tg and
oxygen permeability have been demonstrated when
POSS derivatives are incorporated into polymer
matrices.[94,96,97] In a study by Culbertson et al. three
differentmethods of incorporating amono-methacrylated
POSS into dental compositeswere studied as follows: 1) by
manufacturingPOSS-containingmacromonomers, and co-
polymerization with dental monomers, 2) by using a one
steppolymerisationof POSSwithdentalmonomers, and3)
by developing a POSS co-polymer followed by in situ
polymerisation with dental monomers. The results
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Macromol. Rapid Commun.
� 2011 WILEY-VCH Verlag Gmb
demonstrated that reacting methacrylate POSS into
known dental polymeric formulations significantly
decreased polymer shrinkage, although a slight reduction
in mechanical properties was observed, especially at
loadings greater than 10wt.-%. Their work indicated that
synthesising POSS-containing macromonomers enabled
the improved overall dispersibility of POSS when reacted
with dental monomers.[96,97]
Methacrylated and octaphenyl-POSSmoieties have been
reacted with HEMA (2-hydroxyethylmethacrylate),
BisGMA (bis-phenol A-glycidyldimethacrylate), and
TEGDMA (tetraethylglycidylmethacrylate)-based restora-
tive fillers, and Dodiuk-Kenig et al. compared the effect of
the two different terminal functional groups on POSS by
investigating the thermal, mechanical, and physical
properties. They found that acrylated POSS resulted in a
5 8C increase inTg, a7% increase in compressive strength, an
increase in bond shear strength (36%), and a decrease in
polymer shrinkage by 28%, while incorporation of octa-
phenyl-POSS decreased the compressive strength by 20%,
the bond shear strength by 49%, and polymer shrinkage by
67%. Itwas concluded that themechanical properties of the
dental composites were significantly improved by acry-
lated POSS, but diminished with octaphenyl-grafted POSS,
indicating that the chemical functionality of the side-chain
groups had a strong influence on the dental materials and
their adhesive behaviour.[98]
The main obscurity in developing dental materials with
low polymer shrinkage rates is the shortfall in mechanical
properties to achieve the requirements that are necessary
for clinical use. It hasbeen frequentlymentioned that POSS-
modified polymers can be achieved at relatively low cost
and have good processability, toughness, and thermody-
namic and anti-oxidative surface properties.[99,100]
Recently, Wu et al. evaluated the effect of methacrylated
POSS incorporated into Bis-GMA and TEGDMA dental
composite resins. In this study, POSS was incorporated
into the resins at different weight percentages ranging
between 0 and 15wt.-%. The microstructure was char-
acterised using FT-IR spectroscopy and XRD studies. It was
found that adding 2wt.-% of POSS resulted in improved
mechanical properties with a 15% increase in flexural
strength, a 12% increase in compressive strength, a 15%
increase in hardness, as well as enhanced toughness of the
resins. They concluded that incorporation of as little as
2wt.-% POSS improved themechanical properties of dental
materials.
The influence of POSS on the biocompatibility of
methacrylate-based dental composites was also studied
by Kim et al.[47] In this study, an acrylic-based hybrid
composite with POSS showed improved biocompatibility.
Therefore, taking advantage of the aforementioned proper-
ties and its rigidity, POSS can be used as a potential
candidate in reducing the shrinkage of dental composite
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H. Ghanbari, B. G. Cousins, A. M. Seifalian
materials based on multi-methacrylate functional groups,
as well as improving their biocompatibility confirmed by
metabolic and mutagenic studies.[47,96] In a further study
investigating novel dental restorative composites, metha-
cryl-functionalizedPOSS (POSS-MA)wasused to replaceBis-
GMA. The mechanical properties, shrinkage rate, and
degree of double bond conversion of the methacrylates
by photo-polymerization were investigated. The results
demonstrated that a percentage substitution of 10% (or
less) of Bis-GMA with POSS-MA improved the flexural
strength and Young’s modulus, but quantities greater than
25% led to poor mechanical performance, and diminished
properties with a reduced conversion of methacrylate
double bonds, and significantly reduced the rate of photo-
polymerization.[38]
The use of POSS for dental composites in both hard and
soft lining materials highlights a challenging and promis-
ing area that warrants future investigation. Although, it
should be stressed that the uniform dispersion of POSS
throughout the polymeric matrix and their correct synth-
esis routes to achieve dispersibility needs to be addressed,
as both are crucial in understanding their mechanical
performance and physicochemical properties for their use
indentistry, and their influenceon the cells andhost tissues
in the biological environment.
Biological Sensors
POSS has the unique capability of being combined with a
variety of organic compounds in order to specify its
functionality. The eight vertices of a cubic POSS structure
can bond with different side-chain functional groups such
as amine (�NH2), sulfydryl (�SH), hydroxy (�OH), carboxy
(�COOH), and in particular ammonia (�NH3), which leads
to cationic groups on POSS that have been widely used in
applications such as gene and targeted drug delivery, and
detection of DNA and peptides. In particular, POSS
structures have beenused as probes for detecting biological
macromolecules using resonance light scattering (RLS)
techniques as considered by Zou et al.[39] It was demon-
strated that by adding DNA to an aqueous solution of
cationic POSS that the intensity of RLS at l360 nm was
significantly improved. Thus, the RLS intensity strongly
correlatedwith the increasedamountsofDNAandthis type
of interaction was dependent on the pH value and ionic
strength suggestive that it was primarily electrostatic in
nature. This system has many advantages over conven-
tional techniques as a result of sensitivity and the speed of
data acquisition, and can be potentially used as a probe to
determine the concentration ofDNA. Several types of POSS-
containing networks such as octa-aminophenyl POSS
(cationic POSS) have been employed as new reagents for
RLS studieswithDNAsince theyhavegoodwater solubility,
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� 2011 WILEY-VCH Verlag Gmb
stability in a wide range of pH, and high sensitivity and
selectivity.[39]
Conclusion and Future Perspectives
The emerging field of nanomedicine will continue to
revolutionize current medical practice. The unique proper-
ties of POSS and its ability to be incorporated into a wide
range of biocompatible polymers make POSS an attractive
nanomaterial for a versatile array of applications in
medicine. The application of POSS-containing nanocompo-
sites for cardiovascular biomaterials has been widely
explored with very promising results. As these materials
are safe, biocompatible, compliant, resistant to degrada-
tion, anti-thrombogenic, and haemocompatible, the prob-
ability of microvascular occlusion and thromboembolic
events is sufficiently lowered. In addition, such materials
can be tailored to show resistance to calcification and
enhanced mechanical and surface properties, and may be
capable of grafting biologically active macromolecules to
enhance the adhesion, proliferation, and differentiation of
circulatory stem cells into endothelial cells, which are
amongtheotheradvantagesofusingPOSSnanocomposites
in the development of cardiovascular devices. Enhanced
biocompatibility of POSS nanomaterials can be merged
withunique featuresofothernanoparticulate systemssuch
as quantum dot nanocrystals, and silver nanoparticles to
develop novel diagnostics and therapeutics for clinical
applications. POSS-basednanocomposites havebeen inten-
sively studied for novel approaches to tissue engineering.
Thesehighly biocompatiblematerials canbedesignedwith
tunable biodegradation rates and intricate chemistries that
providesuperior scaffolds for tissueengineeringwithmany
different cell types, tissues, and organ systems. Recent
efforts are now being concentrated on using microfabrica-
tion technology and microelectromechanical system
(MEMS) tools to create smart scaffolds that have an
inherent ability and regenerative capacity within the body
for in vivo tissue engineering approaches. If successful, and
in the long run, the clinical implications would offer
significant benefits as the ability to ‘grow’ new tissue in the
laboratory would diminish the need for tissue transfers
during surgery, the transplantation of vital organs, such as
the liver, and would obviate the need for in vivo testing
using animal models. Work continues on the use of POSS
nanomaterials indevelopingbreast implants, drugdelivery
systems, dental materials, biological sensors, and other
areas related to nanomedicine. The immense potential of
POSS nanomaterials for a wide range of biomedical
applications has now opened up new horizons into the
emerging field of nanomedicine with bright future
prospects.
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A Nanocage for Nanomedicine . . .
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Acknowledgements: The authors thank Yasamin Rafiei Naeeni,Dr. Gaetano Burriesci, Dr. Bala Ramesh, and Arnold Darbyshire ofUCL for very useful comments and suggestions.
Received: March 2, 2011; Published online: May 19, 2011; DOI:10.1002/marc.201100126
Keywords: biomaterials; nanocomposites; nanomedicine;polyhedral oligomeric silsesquioxane; tissue engineering
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