Gold nanorods (AuNRs) show surface plasmon absorption bands in the near-infrared region. This characteristic property has stimulated utilization of gold nanorods as novel nanoprobes for noninvasive bioimaging, such as photoacoustic tomography. Herein, we discuss the synthesis of a series of gold nanorods coated with pH-responsive polymers to investigate the effect of the surface structure and zeta potential of nanoparticles on cellular uptake via a surface charge-mediated endocytic pathway. The surface of the gold nanorods was modified with polyethylene glycol (PEG@AuNR) and tertiary amine derivatives, specifically, diethylaminoethyl ester (1@AuNRs), its amide analog (2@AuNRs), and dimethylaminoethyl ester (3@AuNRs). It was found that the pH-sensitivity of 1@AuNRs was relatively high and the surface was positively charged at lower pH. In contrast, the tertiary amino group of 1@AuNRs was deprotonated to form an electrostatically neutral surface at higher pH. The pH-responsive gold nanorods were incubated with A549 cells (human lung cancer cells) to quantify the amount of cellular uptake using inductively coupled plasma mass spectrometry. The results indicate that 1@AuNRs can be taken up efficiently in the cells, and thereafter, slowly flow out of the cells. Interestingly, only small amounts of the amide analog (2@AuNRs) were taken into the cells, suggesting minor structural changes may affect the interaction between the cell surface and AuNRs. This study highlights a potential application of pH-sensitive nanorods as a probe for bioimaging the acidic environment of tumors.

Single walled carbon nanotubes (SWNTs) possess unique structural and functional properties. Their ability to be functionalized with different biomolecules makes them excellent candidates for biomedical applications like targeted drug delivery and cancer diagnostics. However, prior to use in therapeutic applications, biocompatibility of SWNTs needs to be thoroughly investigated. Blood is a living tissue and contains cells which can potentially interact with SWNTs during the drug delivery process. The interaction of leukocytes in blood with the SWNTs can provide information regarding the immune response of the host to the nanotubes. Here, we evaluated the acute immune response of leukocytes in blood to SWNTs via (a) direct interaction, due to the presence of SWNTs in circulation and (b) indirect interaction, due to the presentation of SWNTs to leukocytes via antigen presenting cells. These SWNTs were non-covalently functionalized with single stranded DNA (ss-DNA) that acts as a surfactant for suspending SWNTs in aqueous solutions and also serves as a backbone for attaching and transporting different biomolecules. Isolation of cells from blood was done using density gradient centrifugation. Early activation markers were used to study the activation of different leukocyte subpopulations and any activation results in changes of these markers. Flow cytometry was done to analyze the different subpopulations. Results of our study demonstrated that ss-DNA functionalized SWNTs do not elicit an immune response from leukocytes in blood via direct or indirect interaction. This intensive study demonstrates the biocompatibility of single walled carbon nanotubes and paves the way for their safe use in drug delivery and cancer therapeutics without cytotoxicity.

A novel nanoparticulated form of the poorly water-soluble anticancer drug paclitaxel (PTX) suitable for intravenous administration has been developed using sonication-assisted layer-by-layer (LbL) assembly. The nanoparticles contain up to 70 wt.% of the drug and consist of 150-180 nm solid crystal paclitaxel cores coated with 20-30 nm thick shells of alternative layers of PEGylated poly-L-lysine and heparin. Dispersions of PTX nanoparticles are stable in different biological solvents at concentrations up to 5 mg/ml. Intravenous administration of the LbL-coated nano-crystalline PTX to mice via tail injection provided the preliminary confirmation of their safety and tolerability.

Enzyme-Linked Immuno-Sorbent Assay (ELISA), and other methods based on the same principle, are sensitive and specific, but they suffer from several disadvantages, such as their inherent complexity and requirement for multiple reagents, incubation and washing steps and require a relatively large sample size. We have adapted a new carbon nanotube field effect transistors (CNT-FET) based platform to capture Escherichia coli antigens using only the capture anti-body showing good correlation with an established ELISA assay contrived positive and negative specimens were used to test the new CNT-FET platform and results were obtained within three minutes per each sample. The test is easy to perform, rapid, and cost efficient making it a valuable screening tool for E. coli. In this study, we looked at the applicability of using CNT field effect transistor based biosensor as a rapid diagnostic platform for Escherichia coli O157:H7. The CNT-FETs platform detected positive E. coli samples in three minutes using only 2.5 μL of sample volume. This low sample volume required by the CNT-FET platform can be especially advantageous for diagnostic tests constricted by limited amount of samples.

Cytotoxicity study of magnetic nanomaterials is a key consideration for biomedical applications. Very little is known about the cytotoxic and anti-cancer effects of nickel nanowires (Ni NWs) on mammalian cells and their interaction with proliferating cancer cells. Current therapeutics do not address the full heterogeneity of pancreatic cancers due to the resistance to apoptosis and does not suffice for a successful treatment. Therefore, synthesis of novel anticancer drugs continues to be a potential topic for pancreatic cancer research. In this study, we have investigated the cellular toxicity and anti-cancer effects of Ni NWs in one of the most aggressive human pancreatic ductal cancer (Panc-1) cell lines with the objective of development of a potential treatment strategy. Ni NWs were fabricated in a custom-made setup utilizing the electrodeposition method. Elemental analysis, crystallographic structure, and morphological properties of the synthesized Ni NWs were investigated using Energy Dispersive X-ray Analysis (EDAX), X-Ray Diffraction (X-RD) and Scanning Electron Microscopy (SEM), respectively. Panc-1 cell cultures were maintained according to a slightly modified American Type Culture Collection (ATCC) protocol. Morphological apoptogenic characteristics assessment of the Ni NWs induced Panc-1 cell was accomplished using phase contrast microscopy (PCM). Two commercially available cytotoxicity procedures including 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and trypan blue (TB) assays were utilized to determine the qualitative and quantitative cytotoxicity and anti-cancer effects of Ni NWs. As a negative control, Panc-1 cells without Ni NWs treatment were used in all experiments. Phase contrast microscopy (PCM) was used to confirm the Ni NWs internalization by Panc-1 cells. Both the MTT and TB assays, qualitatively and quantitatively confirmed the cytotoxic and anti-cancer effects of Ni NWs treated Panc-1 cells in vitro in both concentration and exposure-time dependent manners. We studied the cytotoxic and anti-cancer effects of Ni NWs on Panc-1 cells using novel integrated bionanotechnological approaches to understand the corresponding biological pathway with the objective of developing pancreatic cancer treatment. More specifically, we explored the molecular mechanisms associated with the pathway involved in Ni NWs induced toxicity against Panc-1 cells. Our results demonstrated that Ni NWs show strong candidacy for targeting cell selective applications in pancreatic cancer therapy. Key words: Nickel Nanowires, anti-cancer effects, pancreatic cancer.

The effects of poly (lactic-co-glycolic acid) (PLGA) surface properties on lung epithelial carcinoma cell functions were previously identified. Results demonstrated decreased lung epithelial carcinoma cell vascular endothelial growth factor (VEGF) synthesis on 23 nm surface featured PLGA compared to the PLGA nano-smooth substrates. To investigate the universality of nanopatterned PLGA on inhibiting cancer cell functions, here, breast epithelial adenocarcinoma cell, MCF-7, early functions were determined on different PLGA nanometer surface topographies. Moreover, the viability of healthy breast cells was determined by an MTT assay to investigate the effects of nanopatterning on healthy breast cell growth. Atomic force microscopy (AFM) verified the varied nanotopographies on the PLGA surfaces prepared in this study. Importantly, results demonstrated significantly decreased breast adenocarcinoma cell functions (including decreased proliferation rate and decreased VEGF synthesis) on 23 nm featured PLGA surfaces compared to the other PLGA surface topographies (specifically, nano-smooth, 300 nm and 400 nm surface featured PLGA surfaces). In contrast, healthy breast epithelial cell studies indicated a 24% higher cell proliferation on the 23 nm featured PLGA surfaces compared to all other PLGA samples. In summary, these results provided further insights into understanding the role surface nanotopographies can have on selectively inhibiting cancer cell functions for a wide range of anti-cancer applications.

A thermally-activated micelle consisting of a crystallizable poly(caprolactone), PCL, core and a poly(ethylene glycol), PEG, corona was developed to contain magnetic nanoparticles and anti-cancer agent doxorubicin as well as display a targeting RGD peptide. This system has the potential to target cancer cells, deliver combination hyperthermia and chemotherapy, and offer magnetic resonance imaging contrast. The micelles self-assemble in aqueous solutions and form a crystalline core with a melting transition ranging from 40 to 50 °C, depending on the length of the PCL blocks, with dynamic light scattering showing micelle sizes typically ranging from 20 to 100 nm, depending on block lengths and added drug or nanoparticles. The micelles become unstable as they are heated above their melting point, creating a thermally-activated drug release mechanism. By adding magnetite (Fe3O4) nanoparticles into the PCL core, the micelles can be heated using an externally applied AC magnetic field to induce hyperthermia in combination with the thermally-activated drug release. The polymers and magnetic nanoparticles (MNPs) were synthesized and characterized in our laboratories. The melting transitions of the PCL micelle cores were investigated using microcalorimetry. The heating of nanoparticles and magnetomicelles was conducted using a custom-built hyperthermia coil capable of generating fields of several hundred Oersteds at frequencies ranging from 50 to 450 kHz. Heating of MNPs was maximized at high field intensities. RGD peptides were attached to the PEG corona using maleimide chemistry, and the ability of the RGD-derivatized micelles to target integrin-expressing cells was investigated using fluorescent dye PKH26 to identify the localization of micelles in cultured human kidney (293) cells in vitro. The crystallizable (and meltable) cores in these micelles were designed to overcome drug leakage common in liposome systems and release the drug on demand after a period of time for localization to integrin receptors.

Hybrid magnetic/plasmonic nanoparticles possess properties originating from each individual material. Such properties are beneficial for biological applications including bio-imaging, targeted drug delivery, in vivo diagnosis and therapy. Limitations regarding their stability and toxicity, however, challenge their safe use. Here, the one-step flame synthesis of composite SiO2-coated Ag/Fe2O3 nanoparticles is demonstrated. The hermetic SiO2 coating does not influence the morphology, the superparamagnetic properties of the iron oxide particles and the plasmonic optical properties of the silver particles. Therefore, the hybrid SiO2-coated Ag/Fe2O3 nanoparticles exhibit desired properties for their employment in bio-applications.

Iron magnetic nanoparticles were synthesized under an inert atmosphere via the reaction between FeCl3 and NaBH4 in droplets of water in a microemulsion consisting of octane with cetyl trimethylammonium bromide and butanol as surfactants. A thin Fe3O4 layer was produced on the iron nanoparticles using slow, controlled oxidation at room temperature. A silica shell was deposited on the Fe3O4 using 3-aminopropyltrimethoxysilane following the method of Zhang et al. [Mater. Sci. Eng. C 30 (2010) 92–97]. The structure and chemistry of the resulting nanoparticles were studied using variety of methods and their magnetic properties were determined. The diameter of the iron core was typically 8-16 nm, while the thickness of the Fe3O4 shell was 2-3 nm. The presence of the silica layer was confirmed using Fourier transform infra-red spectroscopy and the number of NH2-groups on each nanoparticle was determined based on colorimetric tests using ortho-phthalaldehyde.

Silver (Ag) nanoparticles dispersed in an amorphous silica (SiO2) matrix or coated by a SiO2 layer were synthesized by flame spray pyrolysis (FSP). The coated nanoparticles were produced by using a modified enclosed FSP setup, in which the SiO2 precursor was injected through a ring above the FSP nozzle at various burner-ring-distances (BRDs), after the core Ag nanoparticles had been formed. The produced nanoparticles were characterized by XRD, BET, TEM and UV/vis analysis. The Ag particle size was possible to be controlled by tuning the FSP parameters. For the SiO2 coated nanoparticles, larger Ag core sizes were obtained for higher BRDs. All the produced nanoparticles exhibited the characteristic plasmon resonance frequency of Ag nanoparticles.

Gold nanoparticles (GNPs) with precisely controlled near infrared (NIR) absorption were synthesized by one-step reaction of chloroauric acid and sodium thiosulfate. The NIR absorption wavelengths and average particle size increase with increasing molar ratio of HAuCl4/Na2S2O3. The as-synthesized GNPs consist of different shape and size, including small spherical gold colloids and larger non-spherical gold crystals. The GNPs with good chemical and optical stability only form in a suitable range of the HAuCl4/Na2S2O3 molar ratio. High molar ratio of HAuCl4/Na2S2O3 reduces GNPs stability due to Ostwald ripening. Chitosan coating improves particle stability and allows these GNPs effective ablation for esophageal adenocarcinoma under low power NIR laser radiation.

In this work, nanostructured porous silicon (PSi) hosts, synthesized by electrochemical etching of Si, are designed to carry and release the anti cancer drug, mitoxantrone dihydrochloride (MTX). We study the effect of surface chemistry of the Si scaffold on its properties as a drug carrier. The freshly-etched PSi is modified by surface alkylation using thermal hydrosilylation with 1-dodecene. Fourier-transform infrared spectroscopy and nitrogen adsorption-desorption measurements are employed to characterize the PSi carriers after chemical modification. Both, drug loading efficiency and release kinetics are found to be significantly affected by surface chemistry of the PSi. In vitro cytotoxicity studies on human breast carcinoma (MDA-MB-231) cells show that the MTX released from the PSi hosts maintains its cytotoxic functionality.