Drug-delivery strategies by using template-synthesized nanotubes

Encapsulating drugs within hollow nanotubes offers several advantages, including protection from degradation, the possibility of targeting desired locations, and drug release only under specific conditions. Template synthesis utilizes porous membranes prepared from alumina, polycarbonate, or other materials that can be dissolved under specific conditions. The method allows for great control over the lengths and diameters of nanotubes; moreover, tubes can be constructed from a wide variety of tube materials including proteins, DNA, silica, carbon, and chitosan. A number of capping strategies have been developed to seal payloads within nanotubes. Combining these advances with the ability to target and internalize nanotubes into living cells will allow these assemblies to move into the next phase of development, in vivo experiments.     

碳纳米管在药物和基因转运领域的研究进展

当前,国内外的许多研究小组都致力于开发出新型有效的药物和基因转运系统,用于改善多种治疗因子的药理学作用并降低其毒性。在纳米材料这一类中,碳纳米管（Carbon Nanotubes, CNTs）正逐步引起人们的关注。功能化的CNTs的两个关键优势在于它具有很强的细胞穿透能力和较低的细胞毒性,使其在药物和基因转运领域中的应用成为可能。CNTs可通过形成稳定的共价键或形成以非共价键为基础的超分子结合物来运载肽类、蛋白质、核酸和药物等活性分子,并将其运送至特定的组织、器官中以表达特殊的生物学功能。针对这一研究热点,本文综述了近几年国内外关于碳纳米管在药物和基因转运领域中的应用进展,并探讨了其毒性,以期为这一领域中的研究工作者提供参考。     

Pt(II) complexes immobilized on polymer‐modified magnetic carbon nanotubes as a new platinum drug delivery system

We combine nanotechnology and chemical synthesis to create a novel multifunctional platinum drug delivery vehicle based on magnetic carbon nanotubes (multiwall carbon nanotubes/Fe₃O₄@poly(citric acid)/cis‐[(Pt(1,7‐phenanthroline)(DMSO)Cl₂)]‐b‐poly(ethylene glycol) (MCNTs/FO@PC/Pt(II)‐b‐PEG)) for targeted cancer therapy. MCNTs/FO@PC/Pt(II)‐b‐PEG was conveniently prepared by conjugating cis‐[Pt(1,7‐phenanthroline)(DMSO)Cl₂] complex to MCNTs/FO@PC‐b‐PEG via strong hydrogen‐bonding interactions. In comparison with free cisplatin and Pt(II) complex, MCNTs/FO@PC/Pt(II)‐b‐PEG shows higher solubility in aqueous solution and higher cytotoxicity towards human cervical cancer HeLa cells and human breast cancer MDA‐MB‐231 cells. In vitro release experiments revealed that the platinum drug‐loaded delivery system is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but susceptible to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of loaded drugs. Fluorescence microscopy studies revealed that this magnetic nanohybrid system possesses marked cell‐specific targeting in vitro in the presence of an external magnetic field. The results indicated that the prepared superparamagnetic MCNTs/FO@PC/Pt(II)‐b‐PEG nanohybrid system is a promising candidate for inhibiting the proliferation of cancer cells.     

One-pot triple functionalization of carbon nanotubes

Carbon nanotubes (CNTs) are very promising as carriers for the delivery of bioactive molecules. The multifunctionalization of CNTs is necessary to impart multimodalities for the development of future CNT-based multipotent therapeutic constructs. In this context, we report the first example of covalent trifunctionalization of different types of CNTs. Our strategy is a simple and efficient methodology based on the simultaneous functionalization of the nanotube surface with three different active groups. The reaction is performed in one step by arylation with diazonium salts generated in situ. The CNTs are functionalized with benzylamine moieties blocked with three different protecting groups that can be selectively removed under specific conditions. The trifunctionalized CNTs were characterized by TEM, thermogravimetric analysis, and Raman and UV/Vis/NIR spectroscopy, while the amine loading was determined by using the Kaiser test. The sequential removal of the protecting groups of the amine functions allows the grafting of the molecules of interest on the nanotube surface to be controlled.     

Tuning retention and selectivity in reversed-phase liquid chromatography by using functionalized multi-walled carbon nanotubes

Aim of this work was to explore the possibility of retention and selectivity tuning in reversed-phase liquid chromatography by means of chemically modified multi-walled carbon nanotubes (MWCNTs). These were synthesized by derivatizing pristine MWCNTs with amino-terminated alkyl chains containing polar embedded groups. A novel hybrid material based on functionalized MWCNTs (MWCNTs-R-NH₂) was prepared, characterized and tested. The idea was to design a mixed-mode separation medium basing its sorption properties on the peculiar characteristics of MWCNTs combined with the chemical interactions provided by the functional chains introduced on the nanotube skeleton. MWCNTs-R-NH₂ were easily grafted to silica microspheres by gamma radiation (using a ⁶⁰Co source) in the presence of polybutadiene as the linking agent. The composite was characterized by scanning electron microscopy (SEM) and Brunauer, Emmett and Teller (BET) analysis in terms of structural morphology, surface area and porosity. The MWCNTs-R-NH₂ sorbent was tested as stationary phase. The reversed-phase behaviour was first proved by analysis of alkylbenzenes, while the key role of CNT derivatization in addressing the selectivity/affinity towards the solutes was evidenced by testing three classes of analytes, viz. barbiturates, steroid hormones and alkaloids. These compounds, with different molecular structure and polarity, were here analysed for the first time on CNT-based LC stationary phases. The behaviour of the novel sorbent was compared in terms of retention capability and resolution with that observed using unmodified MWCNTs, pointing out the mixed-mode characteristics of the MWCNTs-R-NH₂ material. The same test mixtures were analysed also on a conventional mono-modal separation sorbent (C18) to highlight the particular behaviour of the (derivatized)MWCNTs-based stationary phases. The novel material showed better performance in separation of polar compounds, i.e. barbiturates and alkaloids, than the unmodified MWCNTs and than the C18 column. Results showed that MWCNT functionalization is powerful to modulate retention/selectivity in reversed-phase liquid chromatography.     

Pharmacia and biological functionalities of nutrient broth dispersed multi-walled carbon nanotubes:A novel drug delivery system

A new drug delivery system was developed using the interaction of nutrient broth treated multi-walled carbon nanotubes(NBT-MWCNTs) and cefotaxime sodium(CTX) as a model.Investigated factors of the drug delivery system include dispersion effect,biocompatibility of NBT-MWCNTs,pharmacodynamic effect and delivery efficiency in vitro.It was found that MWCNTs can be well dispersed in the nutrient broth and stable at least for one week at 4 °C.The formed NBT-MWCNTs suspension scarcely exhibits toxicity to E.coli a...     

Enhanced separation of Compound Xueshuantong capsule using functionalized carbon nanotubes with cationic surfactant solutions in MEEKC

A novel additive of multi‐walled carbon nanotubes (MWNTs) dispersed with cationic surfactants or mixed cationic/anionic surfactants was used for MEEKC separation of eight phenolic compounds, four glycosides, and one phenanthraquinone. In this context, several parameters affecting MEEKC separation were studied, including the dispersion agents of MWNTs, MWNTs content, oil type, SDS concentration, and the type and concentration of cosurfactant. Compared with conventional MEEKC, the addition of all types of MWNTs dispersions using single or mixed cationic surfactant solutions in running buffers was especially useful for improving the separation of solutes tested, as they influenced the partitioning between the oil droplets and aqueous phase due to the exceptional electrical properties and large surface areas of MWNTs. Use of cationic surfactant‐coated MWNTs (6.4 μg/mL) as the additive in a microemulsion buffer (0.5% octanol, 2.8% SDS, 5.8% isopropanol, and 5 mM borate buffer) yielded complete resolution of 13 analytes. The proposed method has been successfully applied for the detection and quantification of the studied compounds in a complex matrix sample (Compound Xueshuantong capsule).     

L-酪氨酸功能化多壁碳纳米管的制备及表征

采用L-酪氨酸作为修饰剂，制备了一种新型功能化的多壁碳纳米管，并对其进行了表征。红外光谱和电化学实验均证实碳纳米管和酪氨酸是通过酰胺键共价键合的。其中，循环伏安实验中0．22V处羧基峰的消失与红外光谱中1717cm^-1处N-酰化氨基酸的-C=O峰相对应，2931和2860cm^-1处的-CH2-的伸缩振动峰的出现证明了产物的形成。     

Determination of explosives based on novel type of sensor using porphyrin functionalized carbon nanotubes

The hydroxide of meso-tetraphenylporphyrin derivatives functionalized carbon nanotubes (CNTs) was fabricated in our research to explore the interaction between porphyrin and explosive. It was turned out that in the formation of grid porphyrin film, carbon nanotubes as a cruciul base materials promoted the electron transfer rate. Most of important, the results also showed that the electrochemical response was enhanced through increasing the number of -OH substitution in porphyrin. Such information provides the platform for a practical strategy for rational design of the sensor of explosives.     

Targeted delivery of proteins by nanosized carriers

Proteic drug administration poses some additional issues as compared with conventional drugs because of protein high molecular weight and short half‐life in plasma. It is well known that protein delivery canbe significantly improved by using targeted nanocarriers. Among the diverse investigated systems, this overview focuses onliposomes and nanoparticles. Indeed, because of their subcellular size, nanocarriers can cross the fenestration of the vascular epithelium and penetrate tissues. Moreover, nanosystems can be confined at the location of choice by conjugation to molecules that strongly bind the target cells. In spite of the significant progress made in the design and engineering of liposomes and nanoparticles tailored to the targeted delivery of proteins, these nanocarriers seldom succeed in delivering proteins directly inside the cell cytosol. Accordingly, some attention is also paid to virosomes and fusion proteins. These systems have a few advantages over conventional nanocarriers, particularly the ability to cross the cell membrane. They also share the main drawback of being highly immunogenic. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1–11, 2008     

Rheology of polycarbonate reinforcedwith functionalized and unfunctionalized single-walled carbon nanotubes

Nanocomposites of polycarbonate (PC) containing low concentrations of pristine and COOH and OH functionalized single-walled carbon nanotubes (SWNTs, COOH-SWNTs and OH-SWNTs) were prepared by melt-mixing and analyzed using rheology and scanning electron microscopy (SEM). The steady state and linear viscoelastic behavior of each nanocomposite material is presented and compared to that of the neat PC. SEM analysis revealed that samples containing functionalized SWNTs were more dispersible than samples containing the pristine SWNTs.     

Effects of functionalized carbon nanotubes in peroxide crosslinking of diene elastomers

The crosslinking reaction of ethylene-propylene-diene terpolymer (EPDM) peroxide vulcanization filled with pristine and functionalized carbon nanotubes (CNTs and S/CNTs) was evaluated by rheometric tests. The functionalization of CNTs was carried out by diazonium salt methodology in acid medium. S/CNTs were characterised by means of TGA, EDX, Raman and elemental analysis. Pristine CNTs were found to gradually increase the delta torque as a function of loading fraction. Nevertheless, the vulcanization time, scorch and optimum cure time hardly varied on addition of CNTs. However, S/CNTs noticeably affected the cure process, reducing the vulcanization time and delta torque. This effect was related to the presence of acid sites on the CNTs surface which reduced the peroxide efficiency. For this reason, triallyl cyanurate (TAC), highly reactive towards free radicals, was used as coagent to increase the crosslinking efficiency without affecting the cure rate or adding scorch.     

Direct determination of bioavailable molybdenum in carbon nanotubes

Bioavailable residual metallic impurities within carbon nanotubes (CNTs) are responsible for the toxicity of CNTs. Herein we present a method for fast, sensitive determination of bioavailable molybdenum residual catalyst impurities within CNTs by using electrochemical oxidation in neutral pH buffers at low potentials. This method is unique because no other method can rapidly distinguish between bioavailable/mobilizable impurities from defects in CNTs and between the total amounts of impurities. This method will be indispensable for future toxicological studies of CNTs.     

Toxicity of graphene oxide and multi-walled carbon nanotubes against human cells and zebrafish

Graphene possesses unique physical and chemical properties, which have inspired a wide range of potential biomedical applications. However, little is known about the adverse effects of graphene on the human body and ecological environment. The purpose of our work is to make assessment on the toxicity of graphene oxide (GO) against human cell line (human bone marrow neuroblastoma cell line and human epithelial carcinoma cell line) and zebrafish (Danio rerio) by comparing the toxic effects of GO with its sister, multi-walled carbon nanotubes (MWNTs). The results show that GO has a moderate toxicity to organisms since it can induce minor (about 20%) cell growth inhibition and slight hatching delay of zebrafish embryos at a dosage of 50 mg/L, but did not result in significant increase of apoptosis in embryo, while MWNTs exhibit acute toxicity leading to a strong inhibition of cell proliferation and serious morphological defects in developing embryos even at relatively low concentration of 25 mg/L. The distinctive toxicity of GO and MWNTs should be ascribed to the different models of interaction between nanomaterials and organisms, which arises from the different geometric structures of nanomaterials. Collectively, our work suggests that GO does actual toxicity to organisms posing potential environmental risks and the result is also shedding light on the geometrical structure-dependent toxicity of graphitic nanomaterials.     

MEKC‐LIF analysis of rhodamine123 delivered by carbon nanotubes in K562 cells

Oxidized single‐walled carbon nanotubes (o‐SWNTs) were employed as the drug carriers to deliver the small molecules of Rhodamine123 (Rho123) into the K562 cells via physical adsorption. However, due to the fluorescence quenching of Rho123 on carbon nanotubes, the quantitative determination of Rho123 in cells is difficult. Based on the MEKC coupled with LIF detection, a quantitative approach was developed for the determination of Rho123 delivered into K562 cells by o‐SWNTs. Where the adsorbed Rho123 on o‐SWNTs could be desorbed by SDS in running buffer and be simultaneously separated with o‐SWNTs due to the differences of their electrophoretic mobility by applying the electric potential at the both ends of capillary. Using this approach, the intracellular uptakes of Rho123 in multidrug‐resistant and multidrug‐sensitive leukemia cells were quantified, and the results showed that o‐SWNTs could be used as the potential drug carriers to deliver small molecules into cells via the physical adsorption along with the circumventing of multidrug resistance of leukemia cells.     

High efficient delivery of siRNA into tumor cells by positively charged carbon dots

Abstract

Nowadays development of safe and simple siRNA delivery system is still a great challenge. Carbon dots have attracted considerable attention in bioimaging, drug delivery, nanosensors, and other fields during the past few years. In this study, we successfully developed carbon dots (TEPA-CDs) as siRNA nanocarriers based on glucose and tetraethylene pentamine. TEPA-CDs have a mean diameter of less than 10?nm and positive charged decoration. TEPA-CDs could condense siRNA into stable complexes without no obvious premature release. Cellular uptake analysis clearly showed that Cy3-labeled siRNA could be uptake by HeLa cells. GFP expression in HeLa-EGFP cells could be significantly inhibited by TEPA-CDs/siRNA complexes. Our study indicated that TEPA-CDs could be used as a siRNA nanocarrier to tumor cells.