Xiaoying Yang

Superparamagnetic graphene oxide–Fe3O4nanoparticles hybrid for controlled targeted drug carriers

A superparamagnetic graphene oxide –Fe3O4nanoparticles hybrid (GO–Fe3O4) was prepared via a simple and effective chemical precipitation method. The amount of loading of Fe3O4 on GO was estimated as 18.6 wt% by atomic absorption spectrometry. The hybrid was then loaded with doxorubicin hydrochloride (DXR) and the loading capacity was as high as 1.08 mg mg−1. Both of the GO–Fe3O4 hybrids before and after loading with DXR can be dispersed well in aqueous solution. They can congregate under acidic conditions and move regularly under the force of an external magnet. Furthermore, the aggregated hybrid can be redispersed to form a stable suspension under basic conditions. These properties make it a potential candidate for controlled targeted drug delivery and release.

Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity

A dual-targeting drug delivery and pH-sensitive controlled release system based on multi-functionalized graphene oxide (GO) was established in order to enhance the effect of targeted drug delivery and realize intelligently controlled release. A superparamagnetic GO–Fe3O4 nanohybrid was firstly prepared via a simple and effective chemical precipitation method. Then folic acid, a targeting agent toward some tumor cells, was conjugated onto Fe3O4 nanoparticlesvia the chemical linkage with amino groups of the 3-aminopropyl triethoxysilane (APS) modified superparamagnetic GO–Fe3O4 nanohybrid, to give the multi-functionalized GO. Doxorubicin hydrochloride (Dox) as an anti-tumor drug model was loaded onto the surface of this multi-functionalized GO via π–π stacking. The drug loading capacity of this multi-functionalized GO is as high as 0.387 mg mg−1 and the drug release depends strongly on pH values. Cell uptake studies were carried out using fluorescein isothiocyanate labeled or Dox loaded multi-functionalized GO to evaluate their targeted delivery property and toxicity to tumor cells. The results show that this multi-functionalized GO has potential applications for targeted delivery and the controlled release of anticancer drugs.

Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth

Purpose: To determine whether -CONH-(CH2)6-NH3+Cl− functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. Experimental Design: -CONH-(CH2)6-NH3+Cl− was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. Results: The functionalized SWNTs -CONH-(CH2)6-NH3+Cl− could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. Conclusions: -CONH-(CH2)6-NH3+Cl− functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH2)6-NH3+Cl− functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.

The preparation of functionalized graphene oxide for targeted intracellular delivery of siRNA

Functionalized graphene oxide (GO) for the targeted intracellular delivery of hTERT siRNA was prepared by conjugating GO with polyethylene glycol (PEG) and folic acid, followed by the loading of siRNA with the aid of 1-pyrenemethylamine hydrochloride via π–π stacking. It was found that it could target the HeLa in vitro and the transfected hTERT siRNA could knockdown the protein expression level and mRNA level efficiently.

Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug

The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co-glycidyl methacrylate-co-N,N-bis(acryloyl)cystamine) microspheres were prepared by a two-stage distillation-precipitation polymerization with subsequent surface modification with FA. The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV-vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000 μg mL(-1). The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release.

DNA electrochemical sensor based on an adduct of single-walled carbon nanotubes and ferrocene

A novel electrochemical sandwich-type gene sensing system was designed by using a DNA probe (DNA-probe1) immobilized on a gold electrode, the target DNA, and another DNA probe (DNA-probe2) conjugated on a single-walled carbon nanotubes/ferrocene (Fc–SWNT) adduct. In this sandwich-type gene-sensing electrode, the Fc–SWNT adduct could significantly amplify the electrochemical response of the reduction of H2O2. The target DNA could be detected selectively and sensitively based on the much enhanced electrochemical catalytic property of the Fc–SWNT adduct toward H2O2 reduction.

Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR). To overcome multidrug resistance (MDR) and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep). First, the polymers poly(l-histidine)-coupled polyethylene glycol-2000 (PHIS-PEG2000) and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000) were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000) or 7pep-DSPE-PEG2000 (7-pep HD micelles). The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX), the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr), which attributed to the synergistic effect of poly(l-histidine)-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the target-ability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug-resistant tumors.

Folic acid-conjugated graphene oxide as a transporter of chemotherapeutic drug and siRNA for reversal of cancer drug resistance

Functionalized graphene oxide (GO) with folic acid-conjugated chitosan oligosaccharide (FACO) containing quaternary ammonium groups (GO-FACO+) was successfully prepared. The formation and composition of GO-FACO+ were confirmed by FTIR, UV–Vis, AFM, TGA, and zeta-potential. Cell experiments show that cellular uptake of fluorescein FAM-labeled DNA sequence (FAM-DNA) delivered by GO-FACO+ exhibits higher efficiency in doxorubicin chloride (Dox)-resistant MCF-7 human breast cancer cells (MCF-7/Dox) with folate receptor overexpressed than that delivered by chitosan oligosaccharide (CO)-functionalized graphene oxides (GO-CO+) without folic acid modification and in human lung cancer A549 cells with folate receptor negatively expressed. The loading efficiency of Dox on GO-FACO+ was 568.4xa0μgxa0mg−1 at the initial Dox concentration of 0.5xa0mgxa0mL−1, and in vitro release of Dox showed strong pH dependence. MDR1 siRNA transfected by GO-FACO+ could efficiently knockdown the MDR1 mRNA and P-gp expression levels in MCF-7/Dox cells. GO-FACO+ shows no obvious toxicity even at 500xa0μgxa0mL−1. The sequential deliveries of MDR1 siRNA and Dox by GO-FACO+ exhibited much higher cytotoxicity against MCF-7/Dox cells than only delivery of Dox by GO-FACO+ when Dox concentration is lower than 25xa0μgxa0mL−1, while excess 80xa0% cells were killed in the two cases when Dox concentration is higher than 30xa0μgxa0mL−1. Taken together, this functionalized GO has potential applications for targeted intracellular delivery of anti-tumor drugs and genes.

A novel nanohybrid of daunomycin and single-walled carbon nanotubes: photophysical properties and enhanced electrochemical activity

A nanohybrid adduct of the widely used, functional dye, daunomycin (DM), with single-walled carbon nanotubes (SWNTs) was prepared. Ultraviolet-visible-near infrared and fluorescence spectroscopy and electrochemistry of DM-functionalized SWNTs reveal that DM interacts with SWNTs through strong π–π stacking and there is a significant photo-induced charge-transfer interaction between the two components. Importantly, the novel adduct modified the glassy carbon (GC) electrode to give a much enhanced electrochemical activity than those of DM adsorbed onto not only the bare GC electrode but also the SWNTs-modified GC electrode.

Hyaluronic Acid Stabilized Iodine-Containing Nanoparticles with Au Nanoshell Coating for X-ray CT Imaging and Photothermal Therapy of Tumors

In recent years, considerable efforts have been made for the development of multifunctional nanoparticles with diagnosis and therapy functions. To achieve enhanced CT imaging and photothermal therapy on the tumor, we employed iodinated nanoparticles as template to construct Au nanoshell structure and demonstrated a facile but effective approach to synthesize biocompatible and well-dispersed multifunctional nanoparticles by coating iodinated nanoparticles with Au nanoshell and subsequent surface modification by hyaluronic acid. The resultant poly(2-methacryl(3-amide-2,4,6-triiodobenzoic acid))/polyethylenimine/Au nanoshell/hyaluronic acid (PMATIB/PEI/Au nanoshell/HA) nanoparticles had relatively high X-ray attenuation coefficient and photothermal efficiency. After intravenous injection into MCF-7 tumor-bearing mice, PMATIB/PEI/Au nanoshell/HA nanoparticles were efficiently accumulated in the tumor, remarkably enhanced the tumor CT imaging, and selectively ablated the tumor through the thermal treatment of lesions under the NIR irradiation. Thus, PMATIB/PEI/Au nanoshell/HA nanoparticles displayed a great potential for CT diagnosis and CT-guided, focused photothermal tumor therapy.