Guoying Deng

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.

Degradable rhenium trioxide nanocubes with high localized surface plasmon resonance absorbance like gold for photothermal theranostics

The applications of inorganic theranostic agents in clinical trials are generally limited to their innate non-biodegradability and potential long-term biotoxicity. To address this problem, herein via a straightforward and tailored space-confined on-substrate route, we obtained rhenium trioxide (ReO3) nanocubes (NCs) that display a good biocompatibility and biosafety. Importantly, their aqueous dispersion has high localized surface plasmon resonance (LSPR) absorbance in near-infrared (NIR) region different from previous report, which possibly associates with the charge transfer and structural distortion in hydrogen rhenium bronze (HxReO3), as well as ReO3s cubic shape. Such a high LSPR absorbance in the NIR region endows them with photoacoustic (PA)/infrared (IR) thermal imaging, and high photothermal conversion efficiency (∼57.0%) for efficient ablation of cancer cells. Also, ReO3 NCs show X-ray computed tomography (CT) imaging derived from the high-Z element Re. More attractively, those ReO3 NCs, with pH-dependent oxidized degradation behaviors, are revealed to be relatively stable in hypoxic and weakly acidic microenvironment of tumor for imaging and treatment whilst degradable in normal physiological environments of organs to enable effective clearance. In spite of their degradability, ReO3 NCs still possess tumor targeting capabilities. We thus develop a simple but powerful, safe and biodegradable inorganic theranostic platform to achieve PA/CT/IR imaging-guided cancer photothermal therapy (PTT) for improved therapeutic efficacy and decreased toxic side effects.

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 nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

Acute paraquat (PQ) poisoning is one of the most common forms of pesticide poisoning. Oxidative stress and inflammation are thought to be important mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge intracellular free radicals directly or indirectly. In this study, we investigated whether porous Se@SiO2 nanospheres could alleviate oxidative stress and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells were used in this study. Rats were categorized into 3 groups: control (n=6), PQ (n=18), and PQ + Se@SiO2 (n=18). The PQ and PQ + Se@SiO2 groups were randomly and evenly divided into 3 sub-groups according to different time points (24, 48 and 72 h) after PQ treatment. Porous Se@SiO2 nanospheres 1 mg/kg (in the PQ + Se@SiO2 group) were administered via intraperitoneal injection every 24 h. Expression levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), tumor necrosis factor-α and interleukin-1β were detected, and a histological analysis of rat lung tissues was performed. The results showed that the levels of ROS, malondialdehyde, NF-κB, p-NF-κB, tumor necrosis factor-α and interleukin-1β were markedly increased after PQ treatment. Glutathione and superoxide dismutase levels were reduced. However, treatment with porous Se@SiO2 nanospheres markedly alleviated PQ-induced oxidative stress and inflammation. Additionally, the results from histological examinations and wet-to-dry weight ratios of rat lung tissues showed that lung damage was reduced after porous Se@SiO2 nanosphere treatment. These data indicate that porous Se@SiO2 nanospheres may reduce NF-κB, p-NF-κB and inflammatory cytokine levels by inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO2 nanospheres may be a therapeutic method for use in the future for PQ poisoning.

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.