Inertial cavitation, namely the rapid expansion and subsequent violent collapse of micron-sized cavities under the effect of ultrasound-induced pressure variations, has widely been considered as an undesirable phenomenon for in-vivo biomedical applications. This is mainly because of its highly stochastic nature and difficulties in its reliable initiation in vivo using moderate ultrasound pressure levels. Methods of lowering the pressure required to initiate cavitation, which is known as the cavitation threshold, has been previously addressed with the use of ultrasound contrast agents in form of encapsulated stabilized micron sized bubbles. However, such agents do not readily extravasate into tumours and other target tissues due to their relatively large size. This paper investigates the engineering of core-shell nanoparticles and examines their ability to initiate inertial cavitation in the context of ultrasound-enhanced local drug delivery. The nanoparticulate formulations are size-engineered to target tumour vasculature whilst presenting high surface roughness, facilitating surface air entrapment upon drying. The core-shell nanoparticles have been demonstrated to substantially lower the cavitation threshold in aqueous solution, allowing the initiation of inertial cavitation with moderate ultrasound amplitudes and the low energy levels typically deployed by diagnostic systems. The peak focal pressure where the probability of cavitation is greater than 0.5 was found to decrease by factors of five to ten fold, dependant on particle size, total surface area and surface morphology.

Liposomes (a phospholipid bi-layer which can be formulated to contain drugs or other reagents) composed of endogenous phospholipid dipalmitoylphosphatidylcholine (DPPC) in combination with dioleoylphosphatidylethanolamine (DOPE), lauric acid, and silver sulfadiazine were made into vesicular nanoparticles in this study using an optimized extrusion technique. Liposomes were then tested for antibacterial activity against a range of bacteria species including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Bacillus subtilis (all are relevant human pathogens known to infect implants) and were also challenged to prevent the growth of adherent biofilms (a robust slimy extracellular matrix) through an in vitro assay relevant to device related infections. It was found that all liposomes reduced bacterial growth, and, most importantly, liposomes containing DPPC and DOPE reduced biofilm formation better than the commercially available antibiotic silver sulfadiazine. These results indicated for the first time that such liposomes might be a better approach to prevent device related infections.

Bone fractures are one of the most common bone complications. In more severe cases, bone fixation is accomplished using titanium (Ti) implant materials. Unfortunately, the need for revision surgery often arises due to implant loosening and/or deterioration of the implant/bone interface. Rosette nanotubes (RNTs) are a class of self-assembled organic materials obtained through the self-assembly of a guanine-cytosine hybrid base (G∧C motif). These organic materials have been found to increase osteoblast (bone forming cells) adhesion and hydroxyapatite deposition (bone regeneration) on titanium implants as well as on engineered hydrogels. In order to increase the bioactivity of RNTs to enhance bone cell function on Ti implants, two RNT motifs functionalized with different bioactive deca-peptides (A, B) chosen from the knuckle region of bone morphogenic proteins-7 (BMP-7) were synthesized. Their self-assembly process was investigated in water using UV-Vis and SEM techniques.

Discrete nanoscale tubular architectures have received significant attention during the past decade because of their potential role in electronic and photonic devices, sensors, liquid crystals, artificial channel systems and biomedical engineering [1-2]. Our research group has reported the synthesis and characterization of the bicyclic G∧C motif, a self complementary DNA base analogue, which undergoes hierarchical self-assembly to form Rosette Nanotubes (RNTs) [3]. The stability of this system depends however, on functional group density (sterics) and net charge (electrostatics) on the RNT surface [5c]. To this end, we have synthesized several G∧C modules bearing oligopeptides with different lengths and net charge and investigated their self-assembling properties.

Particulate zinc oxide (ZnO) is a known antibacterial agent. Studies have shown that reducing the size of ZnO particles to nanoscale dimensions further enhances their antibacterial properties. Polymers, like all biomaterials, run the risk of harboring bacteria which may produce an antibiotic-resistant biofilm. The addition of ZnO nanoparticles, to form a composite material, may reduce undesirable bacteria activity. The purpose of the present in vitro study was to investigate the antibacterial properties of ZnO nanoparticles when incorporated into a polymer biomaterial. Staphylococcus aureus were seeded at a known cell density onto coverslips coated in a film of polyvinyl chloride (PVC) with varying concentrations of ZnO nanoparticles. Samples were cultured for 24 or 72 h. Methods of analysis, including optical density readings and crystal violet staining, indicated a reduced presence of biofilm on ZnO nanoparticle and polymer composites compared to polymer control. Live/dead assays provided images to confirm reduced presence of active bacteria on samples with zinc oxide nanoparticles. Development of this technology may improve biomaterial effectiveness for applications, such as endotracheal tubes and implanted biomaterials, which are prone to bacterial infection.

In the present work the photostability of high-quality CuInS2 based nanocrystals (Zn-Cu-In-S/ZnSe/ZnS and CuInS2/ZnS core/shell nanocrystals) of different sizes and concentrations were investigated at ambient condition both under UV irradiation and in the darkness. The photostability of commercial CdSe/ZnS core/shell nanocrystals were used as reference to compare to that of CuInS2 based nanocrystals. The half-life times of the CuInS2 base nanocrystals are 2-8 times that of the reference which indicates the CuInS2 base NCs we obtained in the present work are very stable, reliable and competent for the application in biomedical fields.

Long distance intercellular communication between astrocytes on nanofibrillar and planar surfaces was investigated by epi-fluorescence microscopy and atomic force microscopy. We found that astrocytes on nanofibrillar surfaces and astrocytes on planar surfaces diverged in apparent cell-cell contact structures. Astrocytes on nanofibrillar surfaces exhibited a “single cellular process” response, while astrocytes on planar surfaces exhibited a filopodial network response. The possibility that astrocytes can sense their geometrical environment and form different cell-to-cell contacts on nanofibrillar versus planar surfaces, with activation of different signaling pathways, is discussed.

Cationic rosette nanotubes (RNTs) were generated by functionalization of selfcomplementary twin guanine-cytosine (G^C) motifs with up to 15 L-lysine residues (Kn.T, n = 1–15). siRNA binding capacity was determined by gel retardation assay on agarose gel. Up to K5.T, siRNA complexation was a function of oligolysine-chain length and mole ratio of Kn.T. At higher Kn.T, local cationic density employed by supramolecular assembly emerged as a contributor to siRNA complexation. We have shown that no effective siRNA binding was achieved with equivalent mole ratios of corresponding oligolysine peptides (not conjugated to the G∧C motif). With K12.T, siRNA complexation gave spherical structures in the range of 200 nm, which was internalized and retained by human cell lines without noticeable cytotoxicity. In this report, we demonstrate for the first time the capacity of the RNTs as siRNA carriers that can be tailored to achieve maximum siRNA loading efficiency without carrier-associated cell toxicity. We anticipate these cationic RNTs to be effective in the delivery of biologicallyfunctional siRNA.

A new photonic structure was demonstrated to achieve strong optical coupling between nanoparticle and photonic molecule by utilizing a notched micro ring resonators. By creating a notch in the ring resonator and putting a nanoparticle inside the notch, large spectral shifts and splittings at nm scale can be achieved, compared to only pm scale observed by fiber tip evanescently coupled to the surface of microsphere, thereby significantly lowered the quality factor requirement for single nanoparticle detection. The ability for sorting the type of nanoparticles due to very different mode shift and splitting behavior of dielectric and metallic nanoparticles is also emphasized.

Rosette nanotubes (RNTs) are obtained through the self-organization of biologically inspired self-complementary guanine-cytosine modules (G∧C motif) under physiological conditions. These architectures can express bioactive molecules on their surface by functionalizing the G∧C motif prior to self-assembly. As a result, RNTs are promising drug delivery vehicles for the treatment of diseases such as cancer and inflammatory disorders. Towards these studies, we have explored the toxicity and immunological response of RNTs and are now focused on understanding their cellular uptake, biological distribution and kinetics in vivo. For these investigations, we need to construct a RNT labeled with a radionuclide that can be followed in vivo by SPECT (single photon emission computed tomography) imaging. In this proceeding, we describe a twin G∧C motif that is functionalized with mercaptoacetyl triglycine (MAG3). This is a well known ligand which is able to form a stable chelate with the radionuclides 99mTc or 186/188Re. In order to develop the chemistry for this radiolabeling strategy for the RNTs, we demonstrate the chelation of the MAG3 functionalized twin-G∧C motif with cold rhenium and investigate the self-assembly properties of the complex into RNTs under aqueous conditions.

Lubricin is an amphiphilic glycoprotein that is found in the synovial fluid [1]. This protein holds promise as an anti-biofouling agent. This study investigated lubricin’s ability to prevent bacterial attachment and proliferation on intraocular lenses. The findings from this study indicated that lubricin is able to reduce the attachment of Staphylococcus aureus to poly (methyl methacrylate) intraocular lens. Lubricin coatings were confirmed on the surfaces after a 2 hour soak by changes in surface energy. Also, lubricin reduced bacterial proliferation.

We have conjugated chloroquine onto nano-sized, thiol-stabilized gold nanoparticles by using 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) / N-hydroxysulfosuccinimide (NHS) chemistry. The formation of gold nanoparticles was confirmed using optical spectra for characteristic surface plasmon band; the average size of gold nanoparticles was found to be 5-7 nm from electron microscopy measurements. The anti-tumor activity of prepared nanocomposite, vis-à-vis chloroquine itself, had been demonstrated using MCF-7 breast cancer cell line. To determine the binding affinity of gold-chloroquine nanocomposites to transport proteins present in blood serum, we studied the binding interaction of gold-chloroquine to bovine serum albumin (BSA), the most abundant plasma protein. The binding was studied by using isothermal titration calorimetry and fluorescence spectroscopy and was analyzed in terms of binding constant, entropy and enthalpy change. The gold-chloroquine nanocomposites were found to interact efficiently with BSA and fluorescence quenching experiments involving Trp212 suggests that the nanocomposites bind at site I of BSA.

Bacterial infection of bone (called osteomyelitis) is of great concern to the medical community. In addition to bone, numerous medical devices are susceptible to microbial colonization when implanted. These infections are chronic since bacteria form a robust adhesion to surfaces, can be protected by sticky slime matrix (called a biofilm) from the body’s immune system (which would otherwise naturally clear the bacteria), and antibiotic treatments may not resolve such infections (due to antibiotic resistance). Here, the multifunctional properties of magnetic nanoparticles (termed here superparamagnetic iron oxide nanoparticles, or SPION) will be explored for their antibacterial activity, magnetic properties, and drug deliverable properties. This study provides a first step towards the development of a new type of pharmaceutical useful for orthopedic or other device related infections by demonstrating physical (magnetic) control of antibiotics towards bacteria and biofilms.

Water stable fluorescent ZnO quantum dots (QDs) have been synthesized by wet chemical route in presence of hydrophilic capping agent polyethyleneimine (PEI) as stabilizing agent. The binding interaction of prepared ZnO QDs is studied with bovine serum albumin (BSA) protein. X-ray diffraction measurement reveals hexagonal wurtzite structure of as synthesized ZnO QDs with an average size 4-6 nm, determined using Scherer’s equation and confirmed by transmission electron microscopy (TEM). The ZnO/PEI QDs exhibit strong yellow-green emission centered at 555 nm (2.23 eV). The interaction between BSA and ZnO/PEI QDs has been studied by using spectroscopic and calorimetric methods. Static mode of tryptophan quenching in BSA by ZnO/PEI QDs indicates that a ground state complex formation is taking place between ZnO/PEI and BSA, where, the week interactions (hydrogen bonding and hydrophobic interaction) are contributing towards the stability of the complex.

The microemulsion method is one of the effective methods for preparing nanoparticles in recent years. It has the advantages of simple apparatus, easy operation and controllable particle size. The precursors of NiO nanoparticles were successfully prepared in TritonX-100/n-hexanol/cyclohexane/water W/O microemulsion system using nickel chloride and ammonia water as raw materials. NiO nanoparticles were obtained after heat treatment of the precursors. The effects of heat treatment on the morphology and size distribution of NiO nanoparticles were systematically investigated. The result showed that the size, morphology and dispersion of NiO nanoparticles in the microemulsion state were much better than that in the state after heat treatment. XRD and TEM also showed the size of the NiO nanoparticles increased largely with the increase of heat treatment temperature.

The objective of the present in vitro research was to determine cardiomyocyte function on poly lactic-co-glycolic acid (50:50 (PLA:PGA); PLGA) with greater amounts of carbon nanofibers (CNFs) and variations in CNF size, for myocardial tissue engineering applications. The addition of CNFs would increase conductivity and strength of pure PLGA. For this reason, different PLGA: CNF ratios (100:0, 75:25, 50:50, 25:75, 0:100 wt.%) were created and conductivity and cytocompatibility properties with human cardiomyocytes were determined. Results showed that PLGA:CNF materials were conductive and that conductivity increased with greater amounts of PLGA added, from 0 S.m-1 for 100:0 wt.% (pure PLGA) to 5.5x10-3 S.m-1 for 0:100 wt.% (pure CNFs) material. Furthermore, results indicated that cardiomyocyte density increased with greater amounts of CNFs of 200nm in diameter in PLGA (up to 25:75 wt.% , PLGA:CNFs). This study, thus, provided an alternative conductive scaffold using nanotechnology which should be further explored for cardiovascular applications.

The intracellular cargo delivery performed by kinesin motor proteins can be biomimetically employed to engineer tailor-made artificial nanotransport systems. Kinesin (expressed on an Escherichia coli system) and microtubules (obtained from the polymerization of tubulin proteins) were prepared and characterized. We report recent results and explore the aim of the construction of biomotor-based NanoElectroMechanical Systems (NEMS) and their potential applications, e.g. as drug delivery systems.

Iron deficiency affects approximately 2 billion people worldwide, especially young women and children. Food fortification with iron is a sustainable approach to alleviate iron deficiency but remains a challenge. Water-soluble compounds with high bioavailability (e.g. the “gold standard” FeSO4) usually cause unacceptable sensory changes in foods, while compounds that are less reactive in food matrices are often less bioavailable. Solubility (and therefore bioavailability) can be improved by increasing the specific surface area (SSA) of the compound, i.e. decreasing its particle size to the nm range. Here, iron oxide-based nanostructured compounds with Mg or Ca are made using scalable flame aerosol technology. Addition of either element increased iron solubility to a level comparable to iron phosphate. Furthermore, these additions lightened the powder color and sensory changes in fruit yoghurt were less prominent than for FeSO4.

This study was aimed to investigate in vitro and in vivo behavior of a Ti6Al7Nb biomaterial with a nanostructured HA-type coating and also the design and realization of a new special knee implant together with a selection of a suitable animal model for preclinical experimentation of the implants.

The metallic material used like substrate alloy for layer deposition was a Ti6Al7Nb alloy obtained by double electron beam melting furnace. In order to obtain a nano-crystalline HA-coating first sodium titanate layer was obtained on the surface and then the implant was immersed in Ringer solution with additional PAW1 biovitroceramic (particles under 20 μm). Different deposition times (5, 10 and 19 days) were employed. Microscopy analysis and corrosion tests of the implants relieves that the nanostructured HA layer after 19 days of immersion shows promising results as regarding the implant employ in preclinical experiments.

After a complex design based on knee bone radiography there has been manufactured two different types of devices for the metallic implants: a metallic plate and a pin. Two plates and two pins were implanted in each animal.

For in vivo experiments the chosen animal model was the mini-pig because of its strong chirurgical resistance and perfect anesthesia toleration. For the testing 10 animals were used for implantation and one for the control. When the plate is implanted the bone has to have a good blood supply after the cut in order to avoid bone to die. All experimented implants were maintained in the animal during six months and periodically inspected. No sign of infection or another problem were observed during this period.

The present paper describes an unconventional approach to fabricate superhydrophilic-superhydrophobic template on the TiO2 nanotube structured film by a combination of electrochemical anodization and photocatalytic lithography. Based on template with extreme wetting contrast, various functional nanostructures micropattern with high resolution have been successfully fabricated. The resultant micropattern has been characterized with scanning electron microscopy, optical microscopy, X-ray photoelectron spectroscopy. It is shown that functional nanostructures can be selectively grown at superhydrophilic areas which are confined by the hydrophobic regions, indicating that the combined process of electrochemically self-assembly and photocatalytic lithography is a very promising approach for constructing well-defined templates for various functional materials growth.