One-pot nucleation, growth, morphogenesis, and passivation of 1.4 nm Au nanoparticles on self-assembled rosette nanotubes.

A one-pot strategy for the nucleation, growth, morphogenesis, and passivation of 1.4 nm Au nanoparticles (NPs) on self-assembled rosette nanotubes (RNTs) is described. Tapping-mode atomic force microscopy, transmission electron microscopy, energy-dispersive X-ray analysis, and selected-area electron diffraction were used to establish the structure and organization of this hybrid material. Notably, we found that the Au NPs formed were nearly monodisperse clusters of Au(55) (1.4-1.5 nm) nestled in pockets on the RNT surface.

Macrophage inflammatory response to self-assembling rosette nanotubes.

Rosette nanotubes (RNTs) are a new class of nanomaterials with significant therapeutic potential. However, societal concerns related to the potential adverse health effects of engineered nanomaterials drew attention towards the investigation of their interaction with the human U937 macrophage cell line. The cells are treated with medium only (control), lysine (50 microg mL(-1)), lysine-functionalized RNTs (RNT-K; 1, 5, and 50 microg mL(-1)), Min-U-Sil quartz microparticles (80 microg mL(-1)), or lipopolysaccharide (1 microg mL(-1)). The supernatant and cells are assayed for cell viability, cytokine protein, and mRNA expression at 1, 6, and 24 h post-treatment. The results indicate that RNT-K activate transcription of proinflammatory genes (interleukin-8 and tumor necrosis factor-alpha (TNF-alpha)) within 1 h, but this effect is not accompanied by protein secretion into the supernatant. The effect of the length of RNTs on human U937 macrophage viability is also investigated. Although both short and long RNT-K exhibit time-dependent effects on TNF-alpha transcription, only the short RNT-K (5 microg mL(-1)) increase TNF-alpha concentration at 6 h relative to the long RNT-K. Moreover, RNT-K (1 and 5 microg mL(-1)) have no effect on cell viability by 24 h. These data indicate that RNT-K do not induce a robust inflammatory response or cytotoxicity in the U937 human macrophage cell line, and therefore could be used for biomedical applications.

Rosette nanotubes show low acute pulmonary toxicity in vivo.

Nanotubes are being developed for a large variety of applications ranging from electronics to drug delivery. Common carbon nanotubes such as single-walled and multi-walled carbon nanotubes have been studied in the greatest detail but require solubilization and removal of catalytic contaminants such as metals prior to being introduced to biological systems for medical application. The present in vivo study characterizes the degree and nature of inflammation caused by a novel class of self-assembling rosette nanotubes, which are biologically inspired, naturally water-soluble and free of metal content upon synthesis. Upon pulmonary administration of this material we examined responses at 24 h and 7d post-exposure. An acute inflammatory response is triggered at 50 and 25 microg doses by 24 h post-exposure but an inflammatory response is not triggered by a 5 microg dose. Lung inflammation observed at a 50 microg dose at 24 h was resolving by 7d. This work suggests that novel nanostructures with biological design may negate toxicity concerns for biomedical applications of nanotubes. This study also demonstrates that water-soluble rosette nanotube structures represent low pulmonary toxicity, likely due to their biologically inspired design, and their self-assembled architecture.

Low inflammatory activation by self-assembling Rosette nanotubes in human Calu-3 pulmonary epithelial cells.

Rosette nanotubes (RNT) are a new class of metal-free organic nanotubes synthesized through self-assembly. Because of the wide range of potential biomedical applications associated with these materials, it is necessary to evaluate their potential in vitro toxicity. Here the cytotoxicity of a lysine-functionalized nanotube (RNT-K) in a human Calu-3 pulmonary epithelial cell line is investigated. The cells were treated with media only (control), lysine (50 mg mL(-1)), RNT-K (1, 5, and 50 microg mL(-1)), Min-U-Sil quartz microparticles (QM; 80 microg mL(-1)), and lipopolysaccharide (LPS; 1 microg mL(-1)). The supernatants were analyzed at 1, 6, and 24 h after treatment for the expression of three proinflammatory mediators: IL-8, TNF-alpha and EMAP-II. Cellular viability determined with the Trypan blue assay is significantly reduced in the QM and high-dose RNT-treated groups. TNF-alpha and EMAP-II are undetectable by enzyme-linked-immunosorbent assay (ELISA) in the supernatant of all groups. Although IL-8 concentrations do not differ between treatments, its concentrations increase with time within each of the groups. Quantitative reverse-transcriptase polymerase chain reaction (qRTPCR) of IL-8 mRNA shows increased expression in the high-dose RNT-treated groups at both 1 and 6 h, while an adhesion molecule, ICAM-1 mRNA, shows the greatest increase at 6 h in the QM-treated group. In summary, RNT-K neither reduces cell viability at moderate doses nor does it induce a time-dependent inflammatory response in pulmonary epithelial cells in vitro.

Helical rosette nanotubes: a biomimetic coating for orthopedics?

Helical rosette nanotubes (HRN) are obtained through an entropically driven self-assembly process of low-molecular-weight synthetic modules under physiological conditions. Counter-intuitively, these materials undergo extensive self-assembly under the effect of temperature, resulting in networks of very long nanotubes. We have previously shown, using an in vitro model, that titanium (Ti) coated with HRN containing a lysine side chain (HRN-K1) displayed enhanced osteoblast (OB) adhesion when compared to uncoated Ti (p < 0.01). Because it has been widely known that proteins play a critical role in OB adhesion on nanophase materials, here we examine OB adhesion on heated (+T) and unheated (-T) HRN-K1-coated Ti under serum (+S, presence of proteins) and serum-free (-S, absence of proteins) conditions. The results demonstrated that (a) while proteins enhanced OB adhesion on +T HRN-K1-coated Ti, they had no effect on -T HRN-K1-coated Ti, suggesting an active role played by the rosette nanotubes in promoting OB adhesion, and (b) under -S conditions, +T HRN-K1 induced the same level of OB adhesion as uncoated Ti under +S conditions, suggesting that +T HRN-K1 acts as a protein substitute. Finally, transmission electron microscopy and atomic force microscopy studies of +T and -T HRN-K1-coated Ti revealed a significant change in surface coverage, density and hierarchical organization of the nanotubes upon heating, which was correlated with their ability to promote cell adhesion.

Helical rosette nanotubes with tunable stability and hierarchy.

The design of nanostructured materials with tunable dimensions and properties that maintain their structural integrity under physiological conditions is a major challenge in biomedical engineering and nanomedicine. Helical rosette nanotubes (HRN) are a new class of materials produced through a hierarchical self-assembly process of low molecular weight synthetic organic modules in water. Here, we describe a synthetic strategy to tune their stability and hierarchy by preorganization of the self-assembling units, control of net charge per unit of nanotube surface area, amphiphilicity, and number of H-bonds per self-assembling module, and through peripheral steric (de)compression. Using these criteria, HRNs with tunable stability and hierarchical architecture were produced from self-assembling modules that (a) persist as individual molecules in solution, (b) self-assemble into HRN but denature at high temperature (<85 degrees C), (c) self-assemble into HRN whose structural integrity persists even in boiling water (>95 degrees C), and (d) self-assemble into well-dispersed short nanotubes, long nanotubes, ribbons, or superhelices. Given the biocompatibility, synthetic accessibility, and chemical and physical tunability of these materials, numerous applications in biomedical engineering, materials science, and nanoscience and technology are envisioned.

Long-range flow-induced alignment of self-assembled rosette nanotubes on Si/SiOx and poly(methyl methacrylate)-coated Si/SiOx.

Helical rosette nanotubes are obtained through the self-assembly of low molecular weight synthetic modules in water. Here we demonstrate that despite their dynamic nature, these materials respond very well to directional fluid flow and assume long-range order on flat substrates. Persistence length, order, and packing of the rosette nanotubes were found to depend dramatically on the surface properties of both the substrate and the nanotubes and vary from well-ordered long-range 2D films to bundled nanotubes or amorphous conglomerates. While flow-induced long-range alignment of dynamic nanostructures is unprecedented, the chemical tunability of the rosette nanotubes is anticipated to offer a versatile means for investigating the basis of interfacial forces in self-assembled organo-silicon devices and their effect on the stability and physical properties of organic nanostructures on electroactive surfaces.