Lingjie Meng

Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes

A targeted drug delivery system that is triggered by changes in pH based on single wall carbon nanotubes (SWCNTs), derivatized with carboxylate groups and coated with a polysaccharide material, can be loaded with the anticancer drug doxorubicin (DOX). The drug binds at physiological pH (pH 7.4) and is only released at a lower pH, for example, lysosomal pH and the pH characteristic of certain tumor environments. By manipulating the surface potentials of the modified nanotubes through modification of the polysaccharide coating, both the loading efficiency and release rate of the associated DOX can be controlled. Folic acid (FA), a targeting agent for many tumors, can be additionally tethered to the SWCNTs to selectively deliver DOX into the lysosomes of HeLa cells with much higher efficiency than free DOX. The DOX released from the modified nanotubes has been shown to damage nuclear DNA and inhibit the cell proliferation.

Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system.

A new type of drug delivery system (DDS) involved chitosan (CHI) modified single walled carbon nanotubes (SWNTs) for controllable loading/release of anti-cancer doxorubicin (DOX) was constructed. CHI was non-covalently wrapped around SWNTs, imparting water-solubility and biocompatibility to the nanotubes. Folic acid (FA) was also bounded to the outer CHI layer to realize selective killing of tumor cells. The targeting DDS could effectively kill the HCC SMMC-7721 cell lines and depress the growth of liver cancer in nude mice, showing superior pharmaceutical efficiency to free DOX. The results of the blood routine and serum biochemical parameters, combined with the histological examinations of vital organs, demonstrating that the targeting DDS had negligible in vivo toxicity. Thus, this DDS is promising for high treatment efficacy and low side effects for future cancer therapy.

One-Pot Synthesis of Highly Magnetically Sensitive Nanochains Coated with a Highly Cross-Linked and Biocompatible Polymer†

The organization and functionalization of nanoparticles into hierarchically ordered nanomaterials has attracted great interest because of their unique structures and their electronic, optical, and magnetic properties. Among the synthetic techniques used, organization of magnetic nanoparticles into one-dimensional (1D) nanostructures is particularly intriguing for both fundamental research and practical applications. Two basic strategies have been proposed to obtain 1D magnetic nanostructures, including the use of nanostructured templates or through a controlled selfassembly process. For the latter approach, magnetic dipole-directed assembly represents a versatile method to fabricate magnetic chainlike structures. However, owing to the weak or negligible anisotropic dipolar interaction between the magnetic building blocks, these ordered structures can hardly be maintained after removal of the external field. In this regard, although well-defined block copolymers or endfunctional polymers have been utilized to stabilize 1D magnetic chains, they suffer from disintegration during rinsing with a good solvent. Cross-linked polymeric shells are able to tackle this obstacle, but the synthesis of these organic cross-linkable surfactants are complicated and time-consuming. The development of a facile method to directly obtain 1D magnetic nanochains coated with cross-linked polymers is however still attractive. Herein we present a facile one-pot synthesis of 1D magnetic nanochains coated with highly cross-linked polymer. Fe3O4-based colloidal nanocrystal clusters (CNCs) were selected as building blocks for 1D nanochains owing to the combination of paramagnetism and remarkable magnetic response. The highly cross-linked polymer poly(cyclotriphosphazene-co-4,4’-sulfonyldiphenol) (PZS) was chosen as the shell for the stabilization and functionalization of the 1D nanochains, and it endows the nanochains good water dispersibility, biocompatibility, and tailored surface chemistry. On account of the 1D assembly and the PZS coating, the nanochains display an enhanced magnetic resonance (MR) sensitivity and biocompatiblility. The synthesis of CNCs@PZS nanochains is illustrated in Scheme 1. The Fe3O4 CNCs were first prepared according to a

Fabrication of gold nano- and microstructures in ionic liquids—A remarkable anion effect

Gold nano- and microstructures such as polyhedral crystals, large single-crystalline nanoplates, hollow trapeziform crystals, holey polyhedra, and dendrites were produced via microwave heating of HAuCl(4).4H(2)O in a variety of ionic liquids (ILs) in the absence of capping agents (polymers or surfactants) or additional reducing agents. The influence of the IL anions and cations on the topology (size, shape, etc.) of gold materials was studied in detail. The anions of the ILs control the topology of materials, whereas the cations used in the experiments exert less influence. It was also found that the HAuCl(4) concentration, reaction temperature, and heating method are key parameters that help to control the topological structures of the gold materials. For example, the thickness of the large single-crystalline nanoplates could be adjusted from 16 to 320 nm by varying the HAuCl(4) concentration and reaction temperature. This easy synthetic approach to gold nano- and microstructures is a seedless, one-step, fast, template-free route that shows good reproducibility and may be further developed to produce other types of metal nanostructures that satisfy specific applications.

Cell Behaviors on Polysaccharide-Wrapped Single-Wall Carbon Nanotubes: A Quantitative Study of the Surface Properties of Biomimetic Nanofibrous Scaffolds

Natural polysaccharides such as amylose (AMY), alginate sodium (ALG), and chitosan (CHI) have been noncovalently wrapped onto single-wall carbon nanotubes (SWCNTs) to give a series of SWCNT scaffolds, termed as AMY-SWCNT, ALG-SWCNT, CHI-SWCNT, and CHI/ALG-SWCNT scaffolds. Compared to purified SWCNTs and oxidized SWCNTs, the polysaccharide-wrapped SWCNTs can well mimic nanofibrous extracellular matrix and significantly enhance cell adhesion and proliferation. The surface properties of the SWCNT scaffolds, such as functional groups, surface charge, and hydrophilicity, can all directly influence the protein adsorption and lead to changes in cellular FAK expression, thus affect the mammalian cell morphology and proliferation. By quantitatively studying the surface properties of these SWCNT scaffolds, it can be concluded that relatively positively charged hydrophilic scaffolds that bear -OH groups can remarkably promote cell growth. Considering all properties, the relatively electrical neutral and hydrophilic AMY-SWCNT scaffolds bearing only -OH groups are able to sustain the highest cell viability after 72 h culturing.

Folate-conjugated PEG on single walled carbon nanotubes for targeting delivery of Doxorubicin to cancer cells.

A highly effective drug carrier is constructed by coating folic acid-terminated poly(ethylene glycol) (PEG-FA) on single walled carbon nanotubes (SWNTs) in a facile non-covalent method. The anti-cancer drug, doxorubicin (DOX), is further loaded on the surface of SWNTs at a very high loading efficiency, 149.3 ± 4.1%. The drug system (DOX/PEG-FA/SWNTs) exhibits excellent stability under neutral pH conditions such as serum, but dramatically releases DOX at reduced pH typical of the tumour environment and intracellular lysosomes and endosomes. With the help of FA, DOX/PEG-FA/SWNTs tend to selectively attach onto cancer cells and enter the lysosomes or endosomes by clathrin-mediated endocytosis. This can greatly improve the pharmaceutical efficiency and reduce potential side effects.

MnO2 nanosheets as an artificial enzyme to mimic oxidase for rapid and sensitive detection of glutathione

Nanozymes are increasingly used as components in assays and diagnostics. Here, we describe a rapid and highly sensitive colorimetric assay for the detection and quantification of glutathione (GSH) employing MnO2 nanosheets as an artificial oxidase. In the assay pale yellow 3,3´,5,5´-tetramethylbenzidine (TMB) is oxidized to a blue product (oxTMB) under catalyzing of MnO2 nanosheets with a significant change in absorption at 650nm. GSH selectively inhibits this reaction with a detection limit of 300nM. The high specificity of inhibition by GSH allows this system to be used to determine the GSH concentrations in human serum samples. The MnO2 nanosheet-based assay is simple, rapid, sensitive and selective for the quantification of GSH and surpasses detection methods based on other MnO2 nanomaterials.

The ionic liquid-associated synthesis of a cellulose/SWCNT complex and its remarkable biocompatibility

Single-walled carbon nanotubes (SWCNTs) wrapped with cellulose have been successfully prepared by the treatment of SWCNTs with a cellulose solution in the ionic liquid 1-butyl-3-methylimidazolium bromide. The obtained SWCNT complex can be dispersed in water, forming a stable solution with excellent biocompatibility. It was found that long cellulose/SWCNT scaffolds could promote the growth of HeLa cells. In suspensions, short cellulose/SWCNTs complexes tend to enter HeLa cells and show little affect on cell proliferation. Therefore, the complexes have potential applications in biomaterial scaffolds and intracellular drug delivery systems.

Fabrication of Dendritic Gold Nanoparticles by Use of an Ionic Polymer Template.

A facile method for the fabrication of dendritic gold nanoparticles (NPs) by use of an ionic polymer template has been developed. In situ generation of an imidazolium-based (cationic) polymer, poly[1-methyl-3-(4-vinylbenzyl)imidazolium], with AuCl4- counteranions is achieved by addition of HAuCl4 into a solution containing poly[1-methyl-3-(4-vinylbenzyl)imidazolium chloride]. Subsequent reduction with NaBH4 in water or in a mixture of ethanol and water affords various NPs depending on the conditions, including large dendritic gold NPs that have been analyzed by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and selected area electron diffraction (SAED). The structures of the dendritic gold NPs were found to depend on the ethanol concentration. Scanning electron microscopy (SEM) images of the ionic polymer reveal that the solvent used to deposit the polymer strongly influences its structure and may be correlated to the structure of the resulting NPs.

NaGdF4:Yb3+/Er3+@NaGdF4:Nd3+@Sodium-Gluconate: Multifunctional and Biocompatible Ultrasmall Core–Shell Nanohybrids for UCL/MR/CT Multimodal Imaging

Multimodal bioimaging nanoparticles by integrating diverse imaging ingredients into one system, represent a class of emerging advanced materials that provide more comprehensive and accurate clinical diagnostics than conventional contrast agents. Here monodisperse and biocompatible core-shell nanoparticles, NaGdF4: Yb(3+)/Er(3+)@NaGdF4:Nd@sodium-gluconate (termed as GNa-Er@Nd), with about 26 nm in diameter were successfully prepared by a facile two step reactions in high boiling solvents, and followed a ligand exchange process with sodium gluconate. The resulting GNa-Er@Nd nanoparticles were well characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectra (FTIR), and zeta potentials. These nanohybrids present brightly dual-wavelength excited upconversion luminescence (UCL) under both 980 and 793 nm laser because of the synergistic effect of Yb(3+)/Er(3+) and Nd(3+). They also exhibited excellent relaxivity parameters (r1) in magnetic resonance imaging (MRI) and Hounsfield units (HU) in X-ray computed tomography (CT) that are comparable to the clinical contrast agents. Therefore, these small and monodisperse nanoparticles provide options to construct a unique platform for potential multimodal UCL/CT/MRI imaging simultaneously.