Jingbo Wu

Acceleration of dermal wound healing by using electrospun curcumin‐loaded poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) fibrous mats

This study prepared a composite scaffold composed of curcumin and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymer using coelectrospinning technology. Incorporation of curcumin into the polymeric matrix had an obvious effect on the morphology and dimension of PCEC/curcumin fibers. The results of in vitro anti-oxidant tests and of the cytotoxicity assay demonstrated that the curcumin-loaded PCEC fibrous mats had significant anti-oxidant efficacy and low cytotoxicity. Curcumin could be sustainably released from the fibrous scaffolds. More importantly, in vivo efficacy in enhancing wound repair was also investigated based on a full-thickness dermal defect model for Wistar rats. The results indicated that the PCEC/curcumin fibrous mats had a significant advantage in promoting wound healing. At 21 days post-operation, the dermal defect was basically recovered to its normal condition. A percentage of wound closure reached up to 93.3 ± 5.6% compared with 76.9 ± 4.9% of the untreated control (p < 0.05). Therefore, the as-prepared PCEC/curcumin composite mats are a promising candidate for use as wound dressing.

In vitro mineralization of hydroxyapatite on electrospun poly(ɛ-caprolactone)–poly(ethylene glycol)–poly(ɛ-caprolactone) fibrous scaffolds for tissue engineering application

In this study, a fibrous scaffold was prepared by electrospinning triblock PCL-PEG-PCL (PCEC) copolymer. Afterwards, in vitro biomimetic mineralization was carried out through incubation of the PCEC fibrous mats in a simulated body fluid (SBF) for different time. The apatite-deposited PCEC composite scaffolds were characterized by using Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM) observation and weighing. Due to the importance of biocompatibility, rat ROS 17/2.8 osteoblasts were cultured on mineralized PCEC scaffolds, and the cell proliferation was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays. The obtained results confirmed that the deposited apatite had the chemical composition and crystalline phase similar to those of hydroxyapatite (HA). After 21 days incubation, the mass increase of PCEC scaffold reached up to 22%. Moreover, in vitro cell culture also confirmed that osteoblasts could attach on the mineralized composite scaffolds, and the HA-deposited PCEC mats had less cytotoxicity. So, the mineralized PCEC composite scaffolds had a great potential for tissue engineering application.

Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering

Magnetic nanoparticles have been one of the most attractive nanomaterials for various biomedical applications including magnetic resonance imaging (MRI), diagnostic contrast enhancement, magnetic cell separation, and targeted drug delivery. Three-dimensional (3-D) fibrous scaffolds have broad application prospects in the biomedical field, such as drug delivery and tissue engineering. In this work, a novel three-dimensional composite membrane composed of the tri-block copolymer poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and magnetic iron oxide nanoparticles (Fe3O4 NPs) were fabricated using electrospinning technology. The physico-chemical properties of the PCEC/Fe3O4 membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Morphological observation using scanning electron microscopy (SEM) showed that the composite fibers containing 5% Fe3O4 nanoparticles had a diameter of 250nm. In vitro cell culture of NIH 3T3 cells on the PCEC/Fe3O4 membranes showed that the PCEC/Fe3O4 fibers might be a suitable scaffold for cell adhesion. Moreover, MTT analysis also demonstrated that the membranes possessed lower cytotoxicity. Therefore, this study revealed that the magnetic PCEC/Fe3O4 fibers might have great potential for using in skin tissue engineering.

Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

PURPOSE To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. METHODS AND MATERIALS Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. RESULTS The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. CONCLUSIONS This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model

Abstract The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. An in vitro release test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect the in vitro antiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPs in vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profile in vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). The in vivo antiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer.

A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma

In this study, Hydroxycamptothecin (HCPT)-loaded micelles were formed in water by the self-assembly of folate (FA)-decorated amphiphilic block copolymer, methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), and achieved a hydrodynamic diameter about of 132 nm. HCPT release from the micelles exhibited no initial burst but showed a sustained release profile. The cytotoxicity and targeting ability of FA conjugated polymeric micelles was investigated by using methylthiazoletetrazolium (MTT) and fluorescence microscopy. We found that FA-conjugated micelles had superior cytotoxicity against HeLa cells compared to non-conjugated micelles, and that they exerted this effect by folate receptor (FR)-mediated endocytosis. In addition, HeLa cells were xenografted into nude mice and subjected to radiotherapy (RT) and/or HCPT-loaded micelle treatment. The antitumor efficacy was detected by analysis of tumor growth delay (TGD) and median survival time. Micro fluorine-18-deoxyglucose PET/computed tomography ((18)F-FDG PET/CT) was performed to assess early tumor response to HCPT-loaded micelles in combination with RT. Analysis of cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation (λ-H2AX) was used to evaluate the mechanism by which HCPT loaded micelles led to radiosensitization. Taken together, the results showed that HCPT-loaded FA decorated micelles efficiently sensitized xenografts in mice to RT, and induced G2/M phase arrest, apoptosis and expression of λ-H2AX.

In vitro and in vivo degradation behavior of n‐HA/PCL‐Pluronic‐PCL polyurethane composites

Scaffolds for bone tissue engineering applications should have suitable degradability in favor of new bone ingrowth after implantation into bone defects. In this study, degradation behavior of polyurethane composites composed of triblock copolymer poly(caprolactone)-poluronic-poly(caprolactone) (PCL-Pluronic-PCL, PCFC) and nanohydroxyapatite (n-HA) was investigated. The water contact angle and water absorption were measured to reveal the effect of n-HA content on the surface wettability and swelling behavior of the n-HA/PCFC composites, respectively. The weight loss in three degradation media with pH value of 4.0, 7.4, and 9.18 was also studied accordingly. Fourier transform infrared analysis, differential scanning calorimeter, X-ray diffraction, thermal-gravimetric analysis, and scanning electron microscopy were used to investigate the change of chemical structure and micromorphology after the n-HA/PCFC composite with 30% HA was degraded for different time intervals. Meanwhile, in vivo degradation was conducted by subcutaneous implantation. The weight loss and morphology change during observation periods were also studied.

In vivo synergistic anti-tumor effect of paclitaxel nanoparticles combined with radiotherapy on human cervical carcinoma

Abstract In this study, our purpose was to explore the synergistic anti-tumor effect and mechanism of paclitaxel nanoparticles (PTX-NPs) combined with radiotherapy (RT) on human cervical carcinoma (HeLa). PTX-NPs were prepared by a solid dispersion method using methoxy poly(ethylene glycol)–poly(ɛ-caprolactone) (MPEG–PCL), which combined with RT exerted a potent and high efficient effect against cervical cancer. In vivo antitumor activity of PTX-NPs combined with RT, was estimated using nude mice carrying Hela cell xenograft tumor. The results were evaluated using microfluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) and immunohistochemistry. The results showed that PTX-NPs possessed a more efficient effect than PTX when combined with RT (p < 0.05). PTX-NPs in combination with RT might inhibit cell proliferation through its action on Ki-67, and decreased micro-vessel density (MVD) associated with CD31 and vascular endothelial growth factor (VEGF). These results suggested that PTX-NPs possessed a synergistic anti-tumor effect against cervical cancer when combined with RT.

Oncogenic role of the TP53-induced glycolysis and apoptosis regulator in nasopharyngeal carcinoma through NF-κB pathway modulation

The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene, which functions to suppress reactive oxygen species (ROS) damage and protect cells from apoptosis. In this study, we investigated the role of TIGAR in nasopharyngeal carcinoma (NPC) tumorigenesis. Imnunohistochemical analysis of the tissue specimens from nasopharyngeal carcinoma patients showed a higher expression level of TIGAR in tumor tissues, compared with normal nasopharyngeal epithelium. Knockdown of TIGAR by lentivirus-shRNA in CNE-2 or 5-8F cells resulted in decreased cell growth, colony formation, migration, invasion, and induced apoptosis. TIGAR overexpression exerted the opposite effects except for apoptosis reduction. In the xenograft tumor models, TIGAR knockdown reduced tumor growth rate and weight, whereas TIGAR overexpression showed the opposite effects. In addition, the NF-κB signaling pathway was decreased in TIGAR silenced cells. In conclusion, our data demonstrated that TIGAR acted as an oncogene in NPC tumorigenesis, and knockdown of TIGAR inhibited NPC tumor growth through the NF-κB pathway.

In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma

Abstract The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). An in vitro release test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES + PTX, and ES-NPs + PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profile in vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs + PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs + PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs.