Xijian Liu

Facile one-pot synthesis of Fe3O4@chitosan nanospheres for MRI and fluorescence imaging guided chemo-photothermal combinational cancer therapy

Multifunctional nanoplatforms that integrate imaging and chemo-photothermal therapy for highly efficient cancer diagnostics and therapeutics have gained great interest in recent years. Herein, we designed and synthesized biodegradable and biocompatible magnetic chitosan nanospheres (Fe3O4@CS) by a facile one-pot synthesis method. Doxorubicin (DOX, an anticancer drug) and indocyanine green (ICG) can be co-loaded into the Fe3O4@CS nanospheres (Fe3O4@CS-ICG/DOX nanocomposites) by virtue of the mesoporous structure and electrostatic interactions of CS. The fabricated nanocomposite showed excellent magnetic resonance imaging (MRI) and fluorescence imaging performances for tumors in vivo. Moreover, chemotherapy and photothermal therapy could be driven simultaneously under NIR laser irradiation. Tumor growth could be effectively inhibited by chemo-photothermal combinational therapy in vivo, achieving excellent synergistic therapeutic efficacy. That is, the proposed biocompatible Fe3O4@CS-ICG/DOX nanocomposites can be used as a kind of multifunctional nanoplatform for MRI and fluorescence imaging guided chemo-photothermal combination cancer therapy.

Selenium nanocomposites as multifunctional nanoplatform for imaging guiding synergistic chemo-photothermal therapy

A multifunctional selenium nanocomposite (selenium@silica core-shell nanoshperes for loading indocyanine green(ICG)/Doxorubicin(DOX)) was fabricated to reach visible and efficient cancer treatment. The Se@SiO2-ICG nanocomposites could be used not only as excellent photothermal agents but also as carriers for DOX delivery. In addition, the Se@SiO2-ICG/DOX nanocomposites exhibited excellent fluorescence imaging and infrared imaging performance. Tumor could be effectively inhibited by Se@SiO2-ICG/DOX due to the triple treatment of photothermal effect and chemotherapy of selenium and DOX. Thus, the Se@SiO2-ICG/DOX nanocomposites have a great potential in imaging guiding synergistic treatment of cancer.

Synthesis and photocatalytic activities of Nd-doped TiO2 mesoporous microspheres

Nd-doped TiO2 mesoporous microspheres with possessing regular micro/nanostructure were synthesized by a simple and facile method. The structure and optical properties of the samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption–desorption isotherms and UV-Visible absorbance spectroscopy. It was revealed that Nd-doped TiO2 mesoporous microspheres are composed of primary nanoparticles with a particle size of ∼25nm. The photocatalytic activities of all the samples were evaluated by degradation methyl orange (MO) in aqueous solution as a model reaction under xenon lamp light irradiation. The results showed that the doped samples demonstrated a higher photocatalytic activity than TiO2 mesoporous microspheres, and the MO of 10mg/mL almost could be completely degraded by the Nd-doped TiO2 mesoporous sample (the dosage of Nd salt to TiO2 is 6%) under xenon lamp light irradiation within 1h.

Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO 2 nanocomposites to suppress reactive oxygen species

Reducing oxidative stress (ROS) have been demonstrated effective for steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH). Selenium (Se) plays an important role in suppressing oxidative stress and has huge potential in ONFH treatments. However the Se has a narrow margin between beneficial and toxic effects which make it hard for therapy use in vivo. In order to make the deficiency up, a control release of Se (Se@SiO2) were realized by nanotechnology modification. Porous Se@SiO2 nanocomposites have favorable biocompatibility and can reduced the ROS damage effectively. In vitro, the cck-8 analysis, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) stain and flow cytometry analysis showed rare negative influence by porous Se@SiO2 nanocomposites but significantly protective effect against H2O2 by reducing ROS level (detected by DCFH-DA). In vivo, the biosafety of porous Se@SiO2 nanocomposites were confirmed by the serum biochemistry, the ROS level in serum were significantly reduced and the curative effect were confirmed by Micro CT scan, serum Elisa assay (inflammatory factors), Western blotting (quantitative measurement of ONFH) and HE staining. It is expected that the porous Se@SiO2 nanocomposites may prevent steroid-induced ONFH by reducing oxidative stress.

Porous Se@SiO 2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

Background Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy.

Inhibition of cancer cell migration with CuS@mSiO 2 -PEG nanoparticles by repressing MMP-2/MMP-9 expression

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

A novel theranostic agent based on porous bismuth nanosphere for CT imaging-guided combined chemo-photothermal therapy and radiotherapy

In recent years, multifunctional bio-nanomaterials applied as theranostic agents in cancer diagnosis and therapy have attracted great attention due to their powerful functionality. Here, for the first time, we develop a novel theranostic agent based on porous bismuth (pBi) nanospheres for tumor imaging and combined chemotherapy, photothermal therapy (PTT) and radiotherapy (RT). The pBi nanospheres have good biocompatibility due to a polyvinylpyrrolidone (PVP) coating, and have a high photothermal conversion efficiency (η = 48.5%) for PTT. The pBi nanospheres could be used as a radiosensitizer to trigger X-ray deposition and acted as an excellent computed tomography (CT) imaging contrast agent owing to the Bi content. The pBi nanospheres can also be used as a carrier for drug delivery due to their porous structures. Moreover, the thermal effect of the as-produced PTT substantially enhanced the release of doxorubicin (DOX) for chemotherapy, resulting in a synergistic therapeutic effect for complete tumor removal. Meanwhile, treatment with pBi/DOX nanospheres caused no obvious toxicity. Therefore, these multi-functional pBi nanospheres, fabricated by a unique method, have a great promise for application in CT imaging-guided synergetic cancer therapy.

Facile assembling of novel polypyrrole nanocomposites theranostic agent for magnetic resonance and computed tomography imaging guided efficient photothermal ablation of tumors

Multifunctional nanocomposites for image-guided cancer therapy are highly desired in clinical application. Herein, a novel theranostic agent based on gold and ferroferric oxide nanoparticles coating polypyrrole particles (PPy@Fe3O4/Au nanocomposites) for computed tomography (CT) and magnetic resonance (MR) imaging guided photothermal therapy was successfully assembled by a very facile electrostatic adsorption method. PPy@Fe3O4/Au nanocomposites exhibit good biocompatibility in vitro and in vivo. Because of high r2 relaxivity of Fe3O4 and high X-ray attenuation ability of Au, the PPy@Fe3O4/Au nanocomposites exhibited desirable CT and MR imaging performance, which provide more comprehensive and accurate diagnostic information. Moreover, PPy@Fe3O4/Au nanocomposites can efficiently kill cancer cells by hyperthermia with the guiding of CT and MR imaging, even completely ablate tumours. Hence, the electrostatic adsorption assembled PPy@Fe3O4/Au nanocomposites have great potential in clinical application for diagnosing and treating tumour in the future.

Exchangeability of FITC-SiO2 Nanoparticles Between Cancer Cells Increases the Range of Drug Delivery

Drug delivery system studies aim to improve nanoparticle (NP) formulation to enable efficient delivery of NPs to tumors. However, NPs must be transported by blood or through direct injection. How NPs leave the circulatory system and how NPs diffuse into a tumor remain unclear, and this uncertainty is a limitation of drug delivery systems. The intimate connection between these questions and metabolism may be related to their biosafety in vivo. Thus, in this study, classical carrier SiO2 NPs were used as typical transport NPs, and fluorescein isothiocyanate (FITC) was used as the representative drug and tracer. As exosome and tunneling nanotubes (TNTs) are the most relevant mechanism for NP transportation and considering the local situation in a tumor, we focused on identifying this phenomenon and investigating TNTs. In conclusion, we effectively demonstrated that NPs can be transferred from cell to cell. Nanotubes may play an important role in this process.

Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage

Abstract Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO2 nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO2 nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO2 nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO2. And Se@SiO2 has few interference to the therapeutic effect of DOX. Particularly, Se@SiO2 significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO2 in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO2 nanocomposite in the clinical use of DOX.