Size Selective Corona Interactions from Self-Assembled Rosette and Single-Walled Carbon Nanotubes.

Nanoparticle corona phases, especially those surrounding anisotropic particles, are central to determining their catalytic, molecular recognition, and interfacial properties. It remains a longstanding challenge to chemically synthesize and control such phases at the nanoparticle surface. In this work, the supramolecular chemistry of rosette nanotubes (RNTs), well-defined hierarchically self-assembled nanostructures formed from heteroaromatic bicyclic bases, is used to create molecularly precise and continuous corona phases on single-walled carbon nanotubes (SWCNTs). These RNT-SWCNT (RS) complexes exhibit the lowest solvent-exposed surface area (147.8 ± 60 m-1 ) measured to date due to its regular structure. Through Raman spectroscopy, molecular-scale control of the free volume is also observed between the two annular structures and the effects of confined water. SWCNT photoluminescence (PL) within the RNT is also modulated considerably as a function of their diameter and chirality, especially for the (11, 1) species, where a PL increase compared to other species can be attributed to their chiral angle and the RNT's inward facing electron densities. In summary, RNT chemistry is extended to the problem of chemically defining both the exterior and interior corona interfaces of an encapsulated particle, thereby opening the door to precision control of core-shell nanoparticle interfaces.

Enhanced antibiotic activity of ampicillin conjugated to gold nanoparticles on PEGylated rosette nanotubes.

PURPOSE: This work presents the preparation of a nanocomposite of ampicillin-conjugated gold nanoparticles (AuNPs) and self-assembled rosette nanotubes (RNTs), and evaluates its antibacterial properties against two strains of drug-resistant bacteria (Staphylococcus aureus [S. aureus], methicillin-resistant S. aureus [MRSA]). MATERIALS AND METHODS: Small, nearly monodisperse AuNPs (1.43±0.5 nm in diameter) nucleated on the surface of polyethylene glycol-functionalized RNTs in a one-pot reaction. Upon conjugation with ampicillin, their diameter increased to 1.86±0.32 nm. The antibacterial activity of the nanocomposite against S. aureus and MRSA was tested using different concentrations of ampicillin. The cytocompatibility of the nanocomposite was also tested against human dermal fibroblasts. RESULTS: Based on bacterial inhibition studies, the nanocomposite demonstrated enhanced antibiotic activity against both bacterial strains. The minimum inhibitory concentration (MIC) of the nanocomposite against S. aureus was found to be 0.58 µg/mL, which was 18% lower than ampicillin alone. The nanocomposite also exhibited a 20 hrs MIC of 4 µg/mL against MRSA, approximately 10-20 times lower than previously reported values for ampicillin alone. In addition, at concentrations of 4 µg/mL of ampicillin (70 µg/mL of AuNPs), the nanocomposite showed negligible cytotoxic effects. CONCLUSION: Our findings offer a new approach for the treatment of drug-resistant bacteria by potentiating inhibitory effects of existing antibiotics, and delivering them using a non-toxic formulation.

Rosette Nanotubes Alter IgE-Mediated Degranulation in the Rat Basophilic Leukemia (RBL)-2H3 Cell Line.

In this study, the effects of rosette nanotube (RNT) exposure on immune cell viability and function were investigated in vitro using the rat basophilic leukemia (RBL)-2H3 cell line. RBL-2H3 viability was decreased in a dose- and time-dependent manner after lysine-functionalized RNT (K-RNT) exposure. In addition, K-RNTs had a significant effect on RBL-2H3 degranulation. When K-RNT exposure was concurrent with IgE sensitization, 50 and 100 mg l(-1) K-RNTs elicited a heightened degranulatory response compared with IgE alone. Exposure to 50 and 100 mg l(-1) K-RNTs also caused degranulation in RBL-2H3 cells not sensitized with IgE (0 ng ml(-1) IgE). Furthermore, in cells preexposed to K-RNTs for 2 h and subsequently washed, sensitized, and stimulated with IgE, a potentiated degranulatory response was observed. Using confocal laser scanning microscopy and a fluorescein isothiocyanate (FITC)-functionalized RNT construct (termed FITC(1)/TBL(19)-RNT), we demonstrated a strong and direct affiliation between RNTs and RBL-2H3 cell membranes. We also demonstrated cellular internalization of RNTs after 2 h of exposure. Together, these data demonstrate that RNTs may affiliate with the cellular membrane of RBL-2H3 cells and can be internalized. These interactions can affect viability and alter the ability of these cells to elicit IgE-FcεR mediated degranulation.

Self-assembled rosette nanotubes and poly(2-hydroxyethyl methacrylate) hydrogels promote skin cell functions.

The next generation skin of wound healing materials should stimulate skin regeneration by actively promoting appropriate cellular adhesion and proliferation. As materials with novel self-assembling and solidification properties when transitioning from room to body temperatures, rosette nanotubes (RNTs) may be such a proactive material. RNTs resemble naturally occurring nanostructures in the skin (such as collagen and keratin) assembling with noncovalent forces in physiological environments. Presenting desirable bioactive properties, RNTs have been used for various tissue engineering applications including increasing in vivo bone and cartilage regeneration. The objective of the current in vitro study was, for the first time, to improve properties of a commonly used hydrogel (poly(2-hydroxyethyl methacrylate) or pHEMA) for skin regeneration by incorporating one type of novel self-assembled RNTs, called TBL. Results showed for the first time increased keratinocyte and fibroblast proliferation on hydrogels coated with TBLs compared to those not coated with TBL. In this manner, this study provides the first evidence that TBL RNTs are promising for wound healing applications due to their optimal cytocompatibility, solidification, and mechanical properties and, thus, should be further studied for such applications.

Self-assembled rosette nanotubes for incorporating hydrophobic drugs in physiological environments.

Rosette nanotubes (RNTs) are novel, biomimetic, injectable, self-assembled nanomaterials. In previous studies, materials coated with RNTs have significantly increased cell growth (eg, osteoblasts, chondrocytes, and endothelial cells) due to the favorable cellular environment created by RNTs. It has also been suggested that the tubular RNT structures formed by base stacking and hydrophobic interactions can be used for drug delivery, and this possibility has not been studied to date. Here we investigated methods to load and deliver tamoxifen (TAM, a hydrophobic anticancer drug) using two different types of RNTs: single- base RNTs and twin-base RNTs. Drug-loaded RNTs were characterized by nuclear magnetic resonance spectroscopy, diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY NMR), and ultraviolet-visible (UV-Vis) spectroscopy at different ratios of twin-base RNTs to TAM. The results demonstrated successful incorporation of hydrophobic TAM into RNTs. Importantly, because of the hydrophilicity of the outer surface of the RNTs, TAM-loaded RNTs were dissolved in water, and thus have great potential to deliver hydrophobic drugs in various physiological environments. The results also showed that twin-base RNTs further improved TAM loading. Therefore, this study demonstrated that hydrophobic pharmaceutical agents (such as TAM), once considered hard to deliver, can be easily incorporated into RNTs for anticancer treatment purposes.

RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation.

Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif). In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C) and amino acid Lys (K-G∧C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as K(x)/RGDSK(y)-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK-G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous K(x)/RGDSK(y)-RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K9°/RGDSK¹°-RNT. Here we provide the first evidence that intravenous administration of K9°/RGDSK¹°-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K9°/RGDSK¹°-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K9°/RGDSK¹°-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K9°/RGDSK¹°-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.