Intracellular Mutual Amplification of Oxidative Stress and Inhibition Multidrug Resistance for Enhanced Sonodynamic/Chemodynamic/Chemo Therapy.

Emerging noninvasive treatments, such as sonodynamic therapy (SDT) and chemodynamic therapy (CDT), have developed as promising alternatives or supplements to traditional chemotherapy. However, their therapeutic effects are limited by the hypoxic environment of tumors. Here, a biodegradable nanocomposite-mesoporous zeolitic-imidazolate-framework@MnO2 /doxorubicin hydrochloride (mZMD) is developed, which achieves enhanced SDT/CDT/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance. The mZMD decomposes under both ultrasound (US) irradiation and specific reactions in the tumor microenvironment (TME). The mZM composite structure reduces the recombination rate of e- and h+ to improve SDT. MnO2 not only oxidizes glutathione in tumor cells to enhance oxidative stress, but also converts the endogenic H2 O2 into O2 to improve the hypoxic TME, which enhances the effects of chemotherapy/SDT. Meanwhile, the generated Mn2+ catalyzes the endogenic H2 O2 into ·OH for CDT, and acts as magnetic resonance imaging agent to guide therapy. In addition, dissociated Zn2+ further breaks the redox balance of TME, and co-inhibits the expression of P-glycoprotein (P-gp) with generated ROS to overcome drug resistance. Thus, the as-prepared intelligent biodegradable mZMD provides an innovative strategy to enhance SDT/CDT/chemotherapy.

Tumor microenvironment responsive self-cascade catalysis for synergistic chemo/chemodynamic therapy by multifunctional biomimetic nanozymes.

Chemodynamic therapy (CDT) is an emerging approach to treat cancer based on the tumor microenvironment (TME), but its limited content of endogenous hydrogen peroxide (H2O2) weakens the anticancer effects. Herein, a multifunctional biomimetic nanozyme (Se@SiO2-Mn@Au/DOX, named as SSMA/DOX) is fabricated, which undergoes TME responsive self-cascade catalysis to facilitate MRI guided enhanced chemo/chemodynamic therapy. The SSMA/DOX nanocomposites (NCs) responsively degrade in acidic conditions of tumor to release Se, DOX, Au and Mn2+. Mn2+ not only enables MRI to guided therapy, but also catalyzes the endogenous H2O2 into hydroxyl radical (˙OH) for CDT. In addition, the Au NPs continuously catalyze glucose to generate H2O2, enhancing CDT by supplementing a sufficiently reactive material and cutting off the energy supply of the tumor by consuming glucose. Simultaneously, Se enhances the chemotherapy of doxorubicin hydrochloride (DOX) and CDT by upregulating ROS in the tumor cells, achieving remarkable inhibition effect towards tumor. Moreover, SSMA/DOX NCs have good biocompatibility and degradability, which avoid long-term toxicity and side effects. Overall, the degradable SSMA/DOX NCs provide an innovative strategy for tumor microenvironment responsive self-cascade catalysis to enhance tumor therapy.

A biocompatible theranostic agent based on stable bismuth nanoparticles for X-ray computed tomography/magnetic resonance imaging-guided enhanced chemo/photothermal/chemodynamic therapy for tumours.

Cancer is a leading cause of death worldwide and seriously threatens the health of humans. The current clinical treatments for cancer are not efficient and always lead to significant side effects. Herein, a biocompatible and powerful theranostic agent (Bi@mSiO2@MnO2/DOX) is fabricated using a facile stepwise reaction method. The Bi nanoparticles (NPs) are coated by mesoporous silica to protect the Bi NPs from oxidation, which guarantees the stable photothermal effect of the Bi NPs. When the Bi@mSiO2@MnO2/DOX nanocomposites (NCs) accumulate in the tumour site, hyperthermia is generated by Bi NPs under near-infrared (NIR) light irradiation for photothermal therapy (PTT), and the generated heat triggers the release of DOX for chemotherapy in the tumour. In addition, the MnO2 of the NCs responsively catalyses endogenous H2O2 to generate O2, raising the oxygen level to enhance the effect of chemotherapy in the tumour microenvironment (TME), and consumes glutathione (GSH) to produce Mn2+ for magnetic resonance (MR) imaging. Under acidic TME conditions, H2O2 and Mn2+ also produce toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT). Furthermore, the Bi NPs can also be used as excellent contrast agents for X-ray computed tomography (CT) imaging of tumours with a high CT value (6.865 HU mM-1). The Bi@mSiO2@MnO2/DOX NCs exhibit a powerful theranostic performance for CT/MR imaging-guided enhanced PTT/CDT/chemotherapy, which opens a new prospect to rationally design theranostic agents for tumour imaging.

Responsive Degradable Theranostic Agents Enable Controlled Selenium Delivery to Enhance Photothermal Radiotherapy and Reduce Side Effects.

Radiotherapy (RT) is a popular clinical therapy method for extending cancer patient survival, but is hampered by severe side effects and the weak therapy effect. Herein, responsive degradable selenium (Se) theranostic agents (Se@SiO2 @Bi nanocomposites (NCs)) are fabricated, which combine computed tomography (CT) imaging and simultaneously enhance the therapeutic effects of photothermal therapy (PTT) and RT, while reducing the side effects of radiation. The Se@SiO2 @Bi theranostic agents can accumulate at the tumor site, and responsively decompose to releease Se, avoiding systemic toxicity by the element. Se enhances the effect of PTT/RT, simultaneously reducing the side effects of RT. The Se@SiO2 @Bi NCs as CT agents also exhibit significantly enhanced contrast imaging performance due to the high atomic number of Bi. More importantly, the Se@SiO2 @Bi NCs can be rapidly excreted without long-term toxicity, owing to responsive degradation into ultrasmall particles (<5 nm) at the tumor site. In vitro and in vivo results show that the Se@SiO2 @Bi NCs can remarkably inhibit tumor cells, without causing appreciable toxicity during the treatment. This study opens a new perspective in rationally designing responsive degradable theranostic agents for future tumor therapy with enhanced therapeutic efficacy and lesser side effects.

A Selenium Nanocomposite Protects the Mouse Brain from Oxidative Injury Following Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common neurological crisis leading to high mortality and morbidity. Oxidative stress-induced secondary injury plays a critical role in neurological deterioration. Previously, we synthesized a porous Se@SiO2 nanocomposite and identified their therapeutic role in osteonecrosis of the femoral head. Whether this nanocomposite is neuroprotective remains to be elucidated. METHODS: A porous Se@SiO2 nanocomposite was synthesized, and its biosafety was determined using a CCK-8 assay. The neuroprotective effect was evaluated by TUNEL staining, and intracellular ROS were detected with a DCFH-DA probe in SH-SY5Y cells exposed to hemin. Furthermore, the effect of the nanocomposite on cell apoptosis, brain edema and blood-brain barrier permeability were evaluated in a collagenase-induced ICH mouse model. The potential mechanism was also explored. RESULTS: The results demonstrated that Se@SiO2 treatment significantly improved neurological function, increased glutathione peroxidase activity and downregulated malonaldehyde levels. The proportion of apoptotic cells, brain edema and blood-brain barrier permeability were reduced significantly in ICH mice treated with Se@SiO2 compared to vehicle-treated mice. In vitro, Se@SiO2 protected SH-SY5Y cells from hemin-induced apoptosis by preventing intracellular reactive oxygen species accumulation. CONCLUSION: These results suggested that the porous Se@SiO2 nanocomposite exerted neuroprotection by suppressing oxidative stress. Se@SiO2 may be a potential candidate for the clinical treatment of ICH and oxidative stress-related brain injuries.

Microbial metabolomics and network analysis reveal fungistatic effect of basil (Ocimum basilicum) oil on Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE: Fungal infections remain a serious problem worldwide that require effective therapeutic strategies. Essential oil of basil (Ocimum basilicum L., BEO) being traditionally used extensively for the treatment of bacterial and fungal infection has a long history. However, the potential mechanism of action was still obscure, especially from the metabolic perspective. MATERIALS AND METHODS: The fungistatic effect of BEO on Candida albicans (C. albicans) was evaluated by measurement of minimum inhibitory concentration (MIC) and morphological analysis. A high-coverage microbial metabolomics approach was utilized to identify the alterations of intracellular metabolites of C. albicans at mid-logarithmic growth phase in response to the subinhibitory concentration of BEO, by using gas chromatography coupled to time-of-fight mass spectrometry (GC-TOFMS). Following the metabolic fingerprinting, systematic network analysis was performed to illustrate the potential mechanism of BEO involved in the suppression of C. albicans. RESULTS: The damage in cellular membranes of C. albicans treated by BEO above MIC was observed on the scanning electron microscope (SEM) micrographs. Metabolomics results showed that, among 140 intracellular metabolites identified by comparison with reference standards, thirty-four had significantly changed abundances under 0.2 MIC of BEO treatment, mainly involving in central carbon metabolism (glycolysis/gluconeogenesis, pentose phosphate pathway and TCA cycle), amino acids, polyamines and lipids metabolism. Pathway and network analyses further found that fifteen ingredients of BEO mainly terpenoids and phenyl-propanoids, potentially participated in the metabolic regulation and may be responsible for the suppression of C. albicans. CONCLUSIONS: The findings highlighted that integrated microbial metabolomics and network analyses could provide a methodological support in understanding the functional mechanisms of natural antimicrobial agents and contribute to drug discovery.

Mitochondria-Modulating Porous Se@SiO2 Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury.

BACKGROUND: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. METHODS: The protective effect of Se@SiO2 NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of Se@SiO2 NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model. RESULTS: This study demonstrated that Se@SiO2 NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of Se@SiO2 was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our Se@SiO2 NPs in various metabolic disorders and inflammatory diseases. CONCLUSION: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders.

Se@SiO2@Au-PEG/DOX NCs as a multifunctional theranostic agent efficiently protect normal cells from oxidative damage during photothermal therapy.

Photothermal therapy (PTT) is a promising treatment for tumors due to its efficiency and non-invasiveness. However, during the PTT treatment, reactive oxygen species (ROS) are produced in response to hyperthermia and thus harm the neighboring normal cells. In this work, a multifunctional theranostic agent (Se@SiO2@Au-PEG/DOX NCs) was exploited to solve this problem by introducing selenium, which can efficiently prevent normal cells from oxidative damage by scavenging reactive oxygen species during photothermal therapy. In addition, the Se@SiO2@Au-PEG/DOX nanocomposites (NCs) not only exhibited excellent properties of combined chemo-thermal synergistic therapy, but also showed no appreciable toxicity towards normal tissues due to the protective effect for continuous release of selenium. Thus, the fabricated Se@SiO2@Au-PEG/DOX NCs provide an integrated solution to overcome the limitations of selenium and PTT, and demonstrate great prospects as a safe and highly reliable theranostic agent.

"All-in-One" Theranostic Agent with Seven Functions Based on Bi-Doped Metal Chalcogenide Nanoflowers.

Most of the existing single-component nanostructures cannot provide comprehensive diagnostic information, and their treatment strategies always have to combine other therapeutics as a complementary for effective biomedical application. Here, we adopted a facile approach to design a theranostic nanoflower (NF) with robust efficacy for comprehensive tumor diagnosis and quadruple synergistic cancer therapy. The NF is equipped with a metallic hybrid of several functional elements and flower-like superstructures and thus shows excellent in vitro and in vivo theranostic performance. It shows high X-ray attenuation coefficiency for the Bi element, strong near-infrared (NIR) plasmon absorbance and singlet oxygen (1O2) generation ability for the Mo element, and great photothermal conversion efficiency (54.7%) because of enhanced photoabsorption of the petal structure. Moreover, the NF realizes a very high doxorubicin-loading efficiency (90.0%) and bimodal pH/NIR-responsive drug release, posing a promise as a controlled drug carrier. The NF also shows excellent performance at trimodal magnetic resonance/X-ray computed tomography/photoacoustic imaging for comprehensive tumor diagnosis. To our best knowledge, it is the first time that integrating at least seven functions into one biomedical nanomaterial for well-rounded tumor theranostics has been reported. This "all-in-one" NF opens a new perspective in developing novel and efficient multifunctional nanotheranostics.

Porous Se@SiO2 nanospheres attenuate cisplatin-induced acute kidney injury via activation of Sirt1.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Porous Se@SiO2 nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model.

Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO2 nanocomposite. The morphology of porous Se@SiO2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO2 nanocomposite. Results: In vitro, intervention with porous Se@SiO2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H2O2-induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO2 nanocomposite may provide clinic benefit for bone tissue engineering.

Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.

Porous Se@SiO2 nanospheres attenuate ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress.

OBJECTIVES: Acute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO2 nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI. METHODS: Male 6- to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO2, I/R + saline, and I/R + Se@SiO2. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO2 nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO2 group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×105 cells/well) and divided into four groups: control + PBS group, control + Se@SiO2 group, H/R + PBS group, and H/R + Se@SiO2 group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues. RESULTS: In vitro, intervention with porous Se@SiO2 nanospheres significantly reduced levels of ROS (P<0.05), inflammatory cytokines (P<0.05), and inflammation-associated proteins (P<0.05). In vivo, tubular damage, cell apoptosis, and interstitial inflammation during AKI were reduced significantly following treatment with porous Se@SiO2 nanospheres. Moreover, the occurrence of fibrosis and tubular atrophy after AKI was attenuated by porous Se@SiO2 nanospheres. CONCLUSION: Porous Se@SiO2 nanospheres exhibited a protective effect in I/R-induced AKI by resisting oxidative stress and inflammation. This suggests that porous Se@SiO2 nanospheres may represent a new therapeutic method for AKI.

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.

Porous Se@SiO2 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-1ß 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-1ß 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-1ß 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.

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.

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

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.

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 ReO3's 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.

Se@SiO2-FA-CuS nanocomposites for targeted delivery of DOX and nano selenium in synergistic combination of chemo-photothermal therapy.

In this study, a versatile tumor-targeted and multi-stimuli-responsive drug delivery vehicle (Se particle@porous silica-folic acid-copper sulfide/doxorubicin (Se@SiO2-FA-CuS/DOX)) was fabricated for combined photothermal therapy with chemotherapy in cancer treatment. Due to excellent targeting ability, the Se@SiO2-FA-CuS/DOX nanocomposites actively accumulated in tumor tissues and thus provided photothermal therapy under NIR irradiation and chemotherapy through the release of DOX and Se. Owing to the synergistic effect of chemotherapy (Se and DOX) and photothermal therapy, the Se@SiO2-FA-CuS/DOX nanocomposites could efficiently inhibit cancer cells both in vitro and in vivo and even completely eliminate tumors. Moreover, as the toxicity of DOX could be reduced by Se, the treatment using Se@SiO2-FA-CuS/DOX nanocomposites exhibited no appreciable adverse reactions. Thus, the Se@SiO2-FA-CuS/DOX nanocomposites have great potential as a multifunctional nanoplatform in future clinical applications.

Porous Se@SiO2 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-1ß 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-1ß 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.