Yinsong Wang

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.

Graphene oxide used as a carrier for adriamycin can reverse drug resistance in breast cancer cells

This study evaluates the reversal effects of graphene oxide (GO) used as a carrier for adriamycin (ADR) in cancer drug resistance, and provides a preliminary investigation into the reversal mechanism. ADR was loaded onto the GO surface (ADR-GO) by physical mixing and drug loading content was found to be high, up to 93.6%. In vitro releases of ADR from ADR-GO were studied using a dialysis method, and they exhibited a significant pH-sensitive property. Cell experiments showed that GO significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher cytotoxicity than free ADR, suggesting that ADR-GO could effectively reverse ADR resistance of MCF-7/ADR, with the reversal index reaching 8.35. Microscopy studies found that GO could effectively carry drug molecules into cells in both endocytosis-dependent and independent manners. In conclusion, use of GO as a carrier for chemotherapeutic agents is favorable for the treatment of drug resistant cancers.

Surface modification of Mitoxantrone-loaded PLGA nanospheres with chitosan

The purpose of this research was to develop polylactic-co-glycolic acid (PLGA) nanospheres surface modified with chitosan (CS). Mitoxantrone- (MTO-) loaded PLGA nanospheres were prepared by a solvent evaporation technique. The PLGA nanospheres surface was modified with CS by two strategies (adsorption and covalent binding). PLGA nanospheres of 248.4+/-21.0 nm in diameter characterized by the laser light scattering technique, scanning electron microscopy (SEM) are spherical and its drug encapsulation efficiency is 84.1+/-3.4%. Zeta potential of unmodified nanospheres was measured to be negative -21.21+/-2.13 mV. The positive zeta potential of modified nanospheres reveals the presence of CS on the surface of the modified nanospheres. Modified nanospheres were characterized for surface chemistry by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR). FT-IR spectra exhibited peaks at 3420 cm(-1) and 1570 cm(-1), XPS spectra shows the N 1s (atomic orbital 1s of nitrogen) region of the surface of the nanospheres, corresponding to the primary amide of CS. In vitro drug release demonstrated that CS-modified nanospheres have many advantages such as prolonged drug release property and decreased the burst release over the unmodified nanospheres, and the modified nanospheres by covalent binding method could achieve the release kinetics of a relatively constant release. These data demonstrate high potential of CS-modified PLGA nanospheres for the anticancer drug carrier.

Graphene oxide can induce in vitro and in vivo mutagenesis

Graphene oxide (GO) has attracted enormous interests due to its extraordinary properties. Recent studies have confirmed the cytotoxicity of GO, we further investigate its mutagenic potential in this study. The results showed that GO interfered with DNA replication and induced mutagenesis at molecular level. GO treatments at concentrations of 10 and 100 μg/mL altered gene expression patterns at cellular level, and 101 differentially expressed genes mediated DNA-damage control, cell apoptosis, cell cycle, and metabolism. Intravenous injection of GO at 4 mg/kg for 5 consecutive days clearly induced formation of micronucleated polychromic erythrocytes in mice, and its mutagenesis potential appeared to be comparable to cyclophosphamide, a classic mutagen. In conclusion, GO can induce mutagenesis both in vitro and in vivo, thus extra consideration is required for its biomedical applications.

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.

Cholesterol succinyl chitosan anchored liposomes: preparation, characterization, physical stability, and drug release behavior

UNLABELLED The purpose of this study was to prepare cholesterol succinyl chitosan anchored liposomes (CALs) and to investigate their characterization, physical stability, and drug release behavior in vitro. Three cholesterol succinyl chitosan (CHCS) conjugates with different substitution degrees (DS) of the cholesterol moiety were synthesized and used as the anchoring materials to coating on the liposome surface by the incubation method. CALs were almost spherical and had a classic shell-core structure. Compared with plain liposomes and chitosan-coated liposomes (CCLs), CALs had larger sizes, higher zeta potentials, and better physical stability after storage at 4 +/- 2 degrees C and 25 +/- 2 degrees C. Epirubicin, as a model drug, was effectively loaded into CALs and exhibited the more sustained release in both phosphate buffer solution (pH 7.4) and 1% (vol/vol) aqueous fetal bovine serum compared to plain liposomes and CCLs. FROM THE CLINICAL EDITOR Cholesterol succinyl chitosan anchored liposomes (CAL) as delivery vehicles are characterized in this work, including their physical stability and drug release behavior in vitro. Epirubicin as a model drug, was effectively loaded into CALs, and exhibited sustained release behavior both in phosphate buffer solution (PBS, pH 7.4) and 1% (V/V) aqueous fetal bovine serum (FBS).

pH-sensitive pullulan-based nanoparticles for intracellular drug delivery

This study reports the design of a novel pH-sensitive nanoparticle carrier based on pullulan for realizing intracellular drug delivery. A series of pullulan derivatives (UCPA) were synthesized by conjugation of both urocanic acid (a pH-sensitive grafted moiety) and cholesterol succinate (a hydrophobically modified moiety) to pullulan. UCPAs exhibited amphiphilic and pH-sensitive properties, and their responding pH value was around 6.5. UCPA nanoparticles prepared by the precipitation method had roughly spherical shapes, and sizes ranging from 150 to 300 nm. Doxorubicin (DOX), as a model antitumor drug, was physically loaded into the UCPA nanoparticles and its in vitro release at different pH values was studied using a dialysis method. UCPA-1 nanoparticles, with the degree of substitution (DS) of urocanyl and cholesterol moieties of 6.8% and 3.5%, respectively, exhibited relatively high drug-loading capability and strong in vitro pH-induced drug release. The results of MTT assays, flow cytometric analyses and confocal microscopy observations confirmed that the UCPA-1 nanoparticles can realize the intracellular delivery of DOX after internalization and enhanced cytotoxicity of DOX against MCF-7 cells.

Deoxycholic acid modified-carboxymethyl curdlan conjugate as a novel carrier of epirubicin: In vitro and in vivo studies

Deoxycholic acid hydrophobically modified-carboxymethylated-curdlan (DCMC) conjugate was developed as a novel carrier for the anticancer drugs. Epirubicin (EPB), as a model drug, was physically loaded into DCMC self-assembled nanoparticles. EPB-loaded DCMC nanoparticles were almost spherical in shape and their size, in the range of 327.4-511.5 nm, increased with the EPB-loading content increasing. In vitro release of EPB from DCMC self-assembled nanoparticles showed sustained drug release pattern and the release rate was related to pH of release media and drug loading content. The cytotoxic activity of EPB-loaded DCMC nanoparticles was assayed by the MTT colorimetric assay. Compared with free drug, EPB-loaded DCMC nanoparticles showed the higher cytotoxicity, which may be attributed to the enhanced cellular uptake. In vivo toxicity study indicated that DCMC conjugate did not induce unexpected side effects. Tissue biodistribution study was performed in tumor-bearing mice. The result showed that DCMC increased the uptake of EPB in the tumor and decreased the uptake of EPB in kidney and heart, compared to free drug. Moreover, tumor volume reductions induced by DCMC conjugate, free EPB and EDNs were 24.3%, 58.9% and 70%, respectively, which suggested that EDNs could effectively retard the growth of the tumor.

pH-sensitive pullulan-based nanoparticle carrier for adriamycin to overcome drug-resistance of cancer cells

Urocanic acid was conjugated to pullulan to synthesize O-urocanyl pullulan (URPA) with degree of substitution (DS) of 8.2%. URPA nanoparticles prepared by dialysis method had spherical shapes and a mean diameter of 156.8 ± 16.8 nm. Adriamycin (ADR) was successfully loaded into URPA nanoparticles and exhibited pH-sensitive in vitro release property. MTT assay showed that ADR-loaded URPA (ADR/URPA) nanoparticles had a significant higher toxicity against drug resistant MCF-7/ADR cells than free ADR, and the reversal index reached up to 9.6. The results of flow cytometry and confocal microscopy showed that URPA nanoparticles efficiently enhanced accumulation and retention of ADR in MCF-7/ADR cells and successfully delivered ADR into cell nucleus. The reversal effect of ADR/URPA nanoparticles on the drug resistance of MCF-7/ADR cells was perhaps related with their cell entry and intracellular drug release mechanisms.