Wenrui Wang

The use of layered double hydroxides as DNA vaccine delivery vector for enhancement of anti-melanoma immune response.

Our previous studies have shown that Mg:Al 1:1 layered double hydroxides (LDH(R1)) nanoparticles could be taken up by the MDDCs effectively and had an adjuvant activity for DC maturation. Furthermore, these LDH(R1) nanoparticles could up-regulate the expression of CCR7 and augment the migration of DCs in response to CCL21. In current study, we have evaluated whether LDH(R1) as DNA vaccine delivery carrier can augment the efficacy of DNA vaccine immunization in vivo. Firstly, we found that LDH(R1) was efficient in combining DNA and formed LDH(R1)/DNA complex with an average diameter of about 80-120 nm. Its high transfection efficiency in vivo delivered with a GFP expression plasmid was also observed. After delivery of pcDNA(3)-OVA/LDH(R1) complex by intradermal immunization in C57BL/6 mice, the LDH(R1) induced an enhanced serum antibody response much greater than naked DNA vaccine. Using B16-OVA melanoma as tumor model, we demonstrated that pcDNA(3)-OVA/LDH(R1) complex enhanced immune priming and protection from tumor challenge in vivo. Furthermore, we showed that LDH(R1) induced dramatically more effective CTL activation and skewed T helper polarization to Th1. Collectively, these findings demonstrate that this LDH(R1)/DNA plasmid complex should be a new and promising way in vaccination against tumor.

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles.

Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.

The in vitro and in vivo anti-tumor effect of layered double hydroxides nanoparticles as delivery for podophyllotoxin

In this research, we intercalated anti-tumor drug podophyllotoxin (PPT) into layered double hydroxides (LDHs) and investigated the in vitro cytotoxicity to tumor cells, the cellular uptake and in vivo anti-tumor inhibition of PPT-LDH. The nanohybrids were prepared by a two-step method with the size of 80-90nm and the zeta potential of 20.3mV. The in vitro cytotoxicity experiment indicated that PPT-LDH nanoparticles show better anti-tumor efficacy than PPT and are more readily taken up by Hela cells. PPT-LDH shows a long-term suppression effect on the tumor growth, and enhances the apoptotic process of tumor cells. The in vivo tests reveal that delivery of PPT via LDH nanoparticles is more efficient, but the mice toxicity of PPT in PPT-LDH hybrids is reduced in comparison with PPT alone. Pharmacokinetics study displays a prolonged circulation time and an increased bioavailability of PPT-LDH than PPT. These observations imply that LDH nanoparticles are the potential carrier of anti-tumor drugs in a range of new therapeutic applications.

Fabrication of magnetite hollow porous nanocrystal shells as a drug carrier for paclitaxel

A facile and simple route is employed to synthesise a new type of magnetite hollow porous nanocrystal shells (HPNSs) as hydrophobic drug delivery vehicles. The morphological evolution of spherical clusters from solid to hollow porous shells is controlled in a straightforward fashion through the reaction time. The obtained magnetite HPNSs possesses high magnetization, well-defined structure, and porous shell, the channels and cavity in HPNSs benefit the drug storage, delivery, and release. The structure of HPNSs was characterized by SEM, TEM and XRD, VSM (vibrating sample magnetometer) data showed that the saturation magnetization values of the Fe3O4 HPNSs are 67.5, 73.2, 79.4, and 88.7 emu/g, corresponding to reaction times of 6, 8, 12, and 16.5 h, respectively. This result clearly proved that the crystallinity could be improved by Ostwald ripening of nanocrystals through a dissolution–recrystallization process, the formation of the hollow porous structure was promoted as well. FT-IR and TGA results showed that the porous shell facilitated paclitaxel diffusion into the cavity of hollow structure, and the drug loading of magnetite HPNSs for paclitaxel is very high (20.2 wt%). The antitumor efficacy of the drug-loaded HPNSs measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was clearly enhanced, compared with free drugs.

Enzyme activity inhibition and secondary structure disruption of nano-TiO2 on pepsin

In this study, the binding and enzyme activity inhibitory effect of nano-TiO(2) on pepsin was explored compared with micro-TiO(2). Nano-TiO(2) was about 60 nm and micro-TiO(2) was about 200 nm, both round in shape. The activity of pepsin was depressed significantly by nano-TiO(2) comparing to micro-ones. The results of UV spectrometry, HPLC, SDS-PAGE and CD assay proved that micro-TiO(2) has only physical absorption effect on pepsin, but no impairment on primary sequences or secondary structure. However, nano-TiO(2) had coordination interaction with pepsin besides physical binding effect. The secondary structure of pepsin was unfolded with the treatment of nano-TiO(2) at pH 6.5 and pH 3.53, which might consequently affect the beta-hairpin loop that protects the active center of pepsin, and then reduce the enzyme activity. Furthermore, the thermodynamic mechanisms of interaction between nano-TiO(2) and pepsin were explored by fluorescence spectrum and ITC analysis. According to the results of thermodynamic analysis, the K value was 3.64x10(6), stoichiometry (N(pepsin:nano-TiO2)) was 3.04x10(3), the total DeltaH was -2277 cal/mol, DeltaS was 22.7 cal/(K mol), therefore the nano-TiO(2)-pepsin interaction is spontaneous. The depression of activity and the unfolding of secondary structure of pepsin were resulted from non-covalent reactions, including electrostatic force and hydrophobic binding. This work studied the different inhibitory effects and revealed mechanisms of the interaction between micro/nano-TiO(2) and pepsin, and provided a useful approach for evaluating the health risk of nano-materials on level of proteins.

Dexamethasone sodium phosphate intercalated layered double hydroxides and their therapeutic efficacy in a murine asthma model

Although inhaled steroids are the first choice to control asthma, frequent corticosteroid administration is associated with many side effects such as adrenocortical suppression, Cushings syndrome and osteoporosis. The purpose of this study was to develop a drug delivery system to overcome the limitation of corticosteroid administration and improve the therapeutic efficacy in an ovalbumin (OVA)-induced allergic asthma rat model. The intercalation of dexamethasone sodium phosphate (Dexa) into layered double hydroxides (LDHs) was achieved by the co-precipitation method and the obtained nanoparticles (Dexa–LDHs) have an average diameter of approximately 100 nm. The X-ray diffraction patterns and FT-IR spectra of the Dexa–LDHs indicated that the Dexa molecules were successfully intercalated into the LDHs via electrostatic interactions. 13C NMR chemical shifts were analysed to clarify the characteristic changes in functional groups after intercalation. Elemental C/H/N and inductively coupled plasma (ICP) analysis revealed the compositions of the nanohybrids. The thermal stability of Dexa anions was enhanced by holding together within the LDHs layers. The drug loading was estimated to be 50.8% and a gradual and biphasic in vitro release behavior of the drugs from LDHs in pH = 7.4 phosphate buffered saline (PBS) was observed. The parabolic diffusion model was used to simulate the release kinetics of Dexa from the LDHs. The potential of Dexa–LDHs as an anti-asthmatic agent was evaluated in the allergic asthma rat model. The results showed that Dexa–LDHs were more effective than Dexa to reduce the number of inflammatory cells in bronchoalveolar lavage (BAL) fluid. Furthermore, Dexa–LDHs significantly inhibited the increase of T-helper-2-type cytokines such as IL-4 and IL-13, and more effectively suppressed airway hyperresponsiveness. In conclusion, these results suggest that Dexa–LDHs could enhance the anti-asthmatic effect of Dexa in the treatment of allergic asthma rats. Our work indicated that LDHs could be a promising candidate for the exploration of new Dexa formulations.

Size-dependent effects of layered double hydroxide nanoparticles on cellular functions of mouse embryonic stem cells

AIM Layered double hydroxide nanoparticles (LDH NPs) are promising for stem cell research and applications. In this study, we investigated the size-dependent interactions of LDH NPs with mouse embryonic stem cells (mESCs). MATERIALS & METHODS LDH NPs with diameters of 100 and 50 nm were synthesized and characterized. mESCs were cultured to undergo spontaneous differentiation. After incubation with LDH NPs, cytotoxicity, cellular uptake, pluripotency, differentiation and epithelial-mesenchymal transition process of mESCs were assessed. RESULTS LDH NPs with the size of 50 nm induced higher cellular uptake and more outstandingly inhibited spontaneous differentiation and epithelial-mesenchymal transition process. CONCLUSION Our research demonstrated the size-dependent effects of LDH NPs on controlling fate and cellular functions of mESCs.