Search

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by immune dysregulation and intestinal inflammation. Rapamycin (Ra), an mTORC1 pathway inhibitor, has shown promise for autophagy induction in IBD therapy but is associated with off-target effects and toxicity. To address these issues, we developed an oral liposome responsive to reactive oxygen species (ROS) using lipids and amphiphilic materials. We combined ketone thiol (TK) for ROS responsive and hyaluronic acid (HA) with high affinity for CD44 receptors to prepare rapamycin-loaded nanoparticle (Ra@TH). Owing to its ROS responsive characteristic, Ra@TH can achieve inflammatory colonic targeting. Additionally, Ra@TH can induce autophagy by inhibiting the mTORC1 pathway, leading to the clearance of damaged organelles, pathogenic microorganisms and oxidative stress products. Simultaneously, it also collaboratively inhibits the NF-κB pathway suppressed by the removal of ROS resulting from TK cleavage, thereby mediating the expression of inflammatory factors. Furthermore, Ra@TH enhances the expression of typical tight junction proteins, synergistically restoring intestinal barrier function. Our research not only expands the understanding of autophagy in IBD treatment but also introduces a promising therapeutic approach for IBD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The tumor microenvironment is a barrier to breast cancer therapy. Cancer-associated fibroblast cells (CAFs) can support tumor proliferation, metastasis, and drug resistance by secreting various cytokines and growth factors. Abnormal angiogenesis provides sufficient nutrients for tumor proliferation. Considering that CAFs express the sigma receptor (which recognizes anisamide, AA), we developed a CAFs and breast cancer cells dual-targeting nano drug delivery system to transport the LightOn gene express system, a spatiotemporal controlled gene expression consisting of a light-sensitive transcription factor and a specific minimal promoter. We adopted RGD (Arg-Gly-Asp) to selectively bind to the αvβ3 integrin on activated vascular endothelial cells and tumor cells. After the LightOn system has reached the tumor site, LightOn gene express system can spatiotemporal controllably express toxic Pseudomonas exotoxin An under blue light irradiation. The LightOn gene express system, combined with multifunctional nanoparticles, achieved high targeting delivery efficiency both in vitro and in vivo. It also displayed strong tumor and CAFs inhibition, anti-angiogenesis ability and anti-metastasis ability, with good safety. Moreover, it improved survival rate, survival time, and lung metastasis rate in a mouse breast cancer model. This study proves the efficacy of combining the LightOn system with targeted multifunctional nanoparticles in tumor and anti-metastatic therapy and provides new insights into tumor microenvironment regulation., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Breast cancer, which requires comprehensive multifunctional treatment strategies, is a major threat to the health of women. To develop multifunctional treatment strategies, we combined photothermal therapy (PTT) with immunotherapy in multifunctional nanoparticles for enhancing the anti-tumor efficacy. Fe 3 O 4 nanoparticles coated with the polydopamine shell modified with polyethylene glycol and cyclic arginine-glycyl-aspartic peptide/anisamide (tNP) for loading the immune adjuvant resiquimod (R848) (R848@tNP) were developed in this research. R848@tNP had a round-like morphology with a mean diameter of 174.7 ± 3.8 nm, the zeta potential of -20.9 ± 0.9 mV, the drug loading rate of 9.2 ± 1.1 %, the encapsulation efficiency of 81.7 ± 3.2 %, high photothermal conversion efficiency and excellent magnetic properties in vitro. Furthermore, this research also explored the anticancer efficacy of nanoparticles against the breast cancer under the near-infrared (NIR) light (808 nm) in vitro and in vivo. R848@tNP-based NIR therapy effectively inhibited the proliferation of breast cancer cells. Moreover, R848@tNP mediated PTT significantly enhanced the maturation of dendritic cells in vitro. Additionally, R848@tNP enhances the anti-tumor effect and evoked an immune response under NIR in vivo. Furthermore, the biosafety of R848@tNP was fully investigated in this study. Collectively, these results clearly demonstrate that R848@tNP, with magnetic resonance imaging characteristics, is a potential therapeutic for breast cancer that combines PTT with the immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of clinical application of MTX, poly (lactic-co-glycolic acid) (PLGA), Eudragits® S100 (ES100), chitosan (CS) and hyaluronic acid (HA) were used to structure the MTX-loaded HA-CS/ES100/PLGA nanoparticles (MTX@hCEP). MTX@hCEP had a hydrodynamic particle size of approximately 202.5 nm, narrow size distribution, negative zeta potential (-18.7 mV), and smooth surface morphology. In vitro drug release experiments under simulated gastrointestinal conditions indicated that MTX@hCEP exhibited colonic pH-sensitive drug release properties. The cellular uptake capacity of hCEP nanoparticles was significantly enhanced in RAW 264.7 macrophages. Moreover, we further found that the MTX@hCEP also inhibited the proliferation and the secretion of pro-inflammatory cytokines in the LPS-stimulated macrophages. In vivo imaging results not only demonstrated that the accumulated in the colon of colitis mice, but also indicated the extended retention time of MTX in the colon. Additionally, MTX@hCEP alleviated inflammatory symptoms via decreasing the activities of myeloperoxidase and pro-inflammatory factors, promoting mucosal repair in vivo. Collectively, these results clearly demonstrated that MTX@hCEP with properties of colon-specific and macrophages targeting can be exploited as an efficient nanotherapeutic for IBD therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine "Zicao" (with an English name Lithospermum erythrorhizon ) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and TGF-β), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD.

Breast cancer is a common malignancy in women. The abnormally dense collagen network in breast cancer forms a therapeutic barrier that hinders the penetration and anti-tumor effect of drugs. To overcome this hurdle, we adopted a therapeutic strategy to treat breast cancer which combined a light-switchable transgene system and losartan. The light-switchable transgene system could regulate expression of the diphtheria toxin A fragment (DTA) gene with a high on/off ratio under blue light and had great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system to achieve tumor microenvironment-responsive and targeted delivery of DTA-encoded plasmids (pDTA) to tumor sites via dual targeting to cluster of differentiation-44 and α v β 3 receptors. In vivo studies indicated that the combination of pDTA and losartan reduce the concentration of collagen type I from 5.9 to 1.9 µg/g and decreased the level of active transforming growth factor-β by 75.0% in tumor tissues. Moreover, deeper tumor penetration was achieved, tumor growth was inhibited, and the survival rate was increased. Our combination strategy provides a novel and practical method for clinical treatment of breast cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Signal amplification is crucial to improve the sensitivity for the electrochemical detection of cardiac troponin I (cTnI), one of the ideal biomarkers for early acute myocardial infarction (AMI) diagnosis. Herein, we developed a novel signal amplification strategy to construct a sandwich-type electrochemical aptasensor for the detection of cTnI. Core-shell Pd@Pt dendritic bimetallic nanoparticles loaded on melamine modified hollow mesoporous carbon spheres (Pd@Pt DNs/NH 2 -HMCS) was prepared as labels to conjugate with thiol-modification DNA aptamers probe for signal amplification. While introducing numerous amino groups, the melamine functionalized hollow mesoporous carbon spheres (NH 2 -HMCS) retained the edge-plane-like defective sites for the adhesion and electrocatalytic reduction of H 2 O 2 . With the unique characteristics of NH 2 -HMCS, it not only enhanced the dispersity and loading capacity of core-shell Pd@Pt dendritic bimetallic nanoparticles (Pd@Pt DNs), but also improved the stability of bonding by the affinity interaction between Pd@Pt DNs and amino groups of melamine. Meanwhile, the synergistic catalysis effect between Pd@Pt DNs and NH 2 -HMCS significantly enhanced the electrocatalytic reduction of H 2 O 2 and further amplified the signal. Under optimal conditions, this recommended aptasensor for cTnI detection displayed a wide dynamic range from 0.1 pg/mL to 100.0 ng/mL and a low detection limit of 15.4 fg/mL (S/N = 3). The sensor also successfully realized the analysis of cTnI-spiked human serum samples, meaning potential applications in AMI diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Current evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). TotalROX (λabs/λem = 425/525 nm) is a ratiometric probe with high detection sensitivity and a superior capacity to monitor total cellular oxidative capacity. Herein, we investigated the potential of combining totalROX with an oral nanoparticle delivery system to detect the degree of colitis. This detection system also featured pH-responsive Eudragit S100, hyaluronic acid with high affinity to the CD44 receptor, and chitosan, and demonstrated improved loading efficiency and stability. An experimental mouse model of experimental colitis was induced by dextran sodium sulfate do that we could investigate the ability of our nanoparticles to target the colon and determine the degree of inflammation. We also determined and validated the positive correlation between the fluorescence intensity of the detection product (Ox670, λabs/λem = 650/675 nm) and myeloperoxidase activity (R 2  = 0.97) and the histopathological score (R 2  = 0.98). TotalROX had significant ability to measure reactive oxygen species (ROS) produced by cells under inflammatory conditions, as confirmed by in vitro experiments with Caco-2 cells. Collectively, the data generated demonstrate that when loaded with totalROX, these functional nanoparticles are promising tools for cellular imaging after oral administration. This is the first description of a ROS-responsive fluorescent probe to evaluate the degree of colitis in experimental animal models and provides a promising approach for the diagnosis of inflammation in IBD with fluorescence-guided colonoscopy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The present study aimed at constructing an oral nanoparticle delivery system loaded with tacrolimus (FK506) for effective treatment of inflammatory bowel disease. A FK506/HP-β-CD inclusion compound was prepared by grinding to increase drug solubility. To address the side- effects in non-target organs and systemic toxicity of FK506, pH-responsive Eudragit S100 (ES100) and hyaluronic acid (HA) with high affinity to CD44 receptor were adsorbed onto the surface of chitosan (CS) nanoparticles loaded with FK506/HP-β-CD through electrostatic interactions to obtain FK506@ES100/HA/CS/HP-β-CD nanoparticles (FK506@EHCh NPs). Caco-2 cells and Raw 264.7 macrophages were used to confirm the lack of cytotoxicity and good uptake ability of the newly generated nanoparticles. FK506@EHCh NPs significantly suppressed secretion of TNF-α, IL-1β and IL-6 by LPS-activated Raw 264.7 macrophages. A dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) murine model was established to further confirm the colon targeting and in vivo efficacy of oral IR-775@EHCh NPs. Based on the collective results, we conclude that packaging FK506 into active targeting nanocarriers sensitive to pH facilitates concentration of the drug within the sites of intestinal inflammation and improves the drug levels in target tissues, thus avoiding systemic side-effects and improving efficacy. In view of the promising results obtained in this study, the potential of EHCh nanoparticles for drug delivery and targeted treatment of inflammatory bowel disease warrants further investigation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gene therapy with external gene insertion (e. g. a suicide gene) and expression specifically in mutated tumor cells has shown to be a promising strategy in treatment of tumors. However, current tumor gene therapy often suffered from low efficiency in gene expression and off-target effects which may cause damage to normal tissues. To address these issues, in this study, a light-switchable transgene nanoparticle delivery system loaded with a diphtheria toxin A (DTA) segment encoded gene, a suicide gene for tumor cells, was developed. The nanoparticles contained vitamin E succinate-grafted polyethyleneimine core and arginylglycylaspartic acid (RGD)-modified pegylated hyaluronic acid shell for targeted delivery of the loaded gene to tumor cells via receptor-mediated (CD44 and αvβ3) endocytosis. Notably, the expression of target proteins in tumor cells could be conveniently regulated by adjusting the blue light intensity in the Light-On system. In in-vitro studies in cultured B16-F10 cells, the pG-DTA-loaded nano-micelles showed greatly improved inhibitory rate compared with the pG-DTA group. Moreover, in the tumor-bearing C57BL/6 mice model, the pG-DTA-loaded nanoparticle exhibited greatly improved efficacy and reduced systemic toxicity with significantly increased survival rate after 21 days. Significantly suppressed tumor angiogenesis was also identified in the nanoparticle-treated group likely due to the targeting ability of the RGD-modified nanoparticle. All the above results indicated that the combination of a light-switchable transgene system with a nanoparticle-based targeted delivery system have great potentials in gene therapy of malignant tumors with improved precision and efficacy., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O 2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen ( 1 O 2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O 2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photodynamic therapy (PDT) utilizes photosensitizers to convert innoxious oxygen to cytotoxic reactive oxygen species under an appropriate light, thus inducing cancer cells necrosis. However, PDT performs in an oxygen-dependent method to destroy cells while hypoxia is a feature for most solid tumors. To effectively improve the PDT effect against solid tumors, an oxygen self-supplying and pH-sensitive therapeutic nanoparticle (PTFC) has been developed by the self-assembly of a tetrakis(pentafluorophenyl) chlorin (TFPC)-conjugated block copolymer (POEGMA- b -P(DEAEMA- co -GMA)). PTFC nanoparticles can transport oxygen to a tumor site with their accumulation in the tumor on account of the good oxygen solubility, therefore relieving the oxygen deficiency of a solid tumor and enhancing the PDT efficacy. It is worth noting that the oxygen loading was realized by the fluorinated photosensitizer itself. In addition, the phototoxicity of PTFC nanoparticles is greatly improved in an acidic aqueous environment due to the DEAEMA unit protonation, which not only enhanced the cellular uptake of nanoparticles but also weakened the aggregation of photosensitizers. Taking the hypoxia and acidic microenvironment of solid tumors, PTFC nanoparticles could be efficiently taken up and disassembled to release oxygen upon accumulation at tumor sites, thus significantly improving the PDT efficacy against solid tumors.

Transition metal phosphates have shown great potential as nanozymes for selective detection of reactive oxygen species (ROS), but its application has been hindered by the complicated synthesis and difficulty in shape and size control. Herein, we present a facile method to fabricate transition metal phosphates by using hollow carbon structures as substrates. Manganese phosphate is a typical Nanozyme used in this design and the shape and size of the Mn x (PO 4 ) y layer can be efficiently controlled by altering the carbon substrates. Characterization demonstrated that Mn x (PO 4 ) y layer modified hollow carbon sphere (Mn-MPSA-HCS) and hollow carbon cubic (Mn-MPSA-HCC) were successfully prepared and used as nanozymes for superoxide detection. The established electrochemical sensor was employed in the online monitoring of drug stimulated superoxide anions released from cancer cells. This method can be adapted as a general way to prepare transition metal phosphate layers with various controllable shapes and sizes as nanozymes for different uses in the future.

Surface charge engineering of nanosized CuS via acidic amino acid modification is proved to be an efficient strategy to realize high peroxidase-mimicking catalytic activity at neutral pH. As a proof-of-concept application, one-pot high-performance colorimetric sensing of glucose by coupling the engineered nanozyme with glucose oxidase is realized.

Selective enrichment and sensitive detection of phosphopeptides are of great significance in many bioapplications. In this work, dendritic mesoporous silica nanoparticles modified with polydopamine and chelated Ti 4+ (denoted DMSNs@PDA-Ti 4+ ) were developed to improve the enrichment selectivity of phosphopeptides. The unique central-radial pore structures endowed DMSNs@PDA-Ti 4+ with a high surface area (362 m 2 g -1 ), a large pore volume (1.37 cm 3 g -1 ), and a high amount of chelated Ti 4+ (75 μg mg -1 ). Compared with conventional mesoporous silica-based materials with the same functionalization (denoted mSiO 2 @PDA-Ti 4+ ) and commercial TiO 2 , DMSNs@PDA-Ti 4+ showed better selectivity and a lower detection limit (0.2 fmol/μL). Moreover, 2422 unique phosphopeptides were identified from HeLa cell extracts with a high specificity (>95%) enabled by DMSNs@PDA-Ti 4+ , better than those in previous reports.

The blood-brain barrier (BBB) restricts the transfer and delivery of most drug substances to brain. In this study, a novel nano-drug delivery system for brain-targeting was developed and investigated in vitro and in vivo. Lactoferrin (Lf) was selected as a brain-targeting ligand and conjugated to β-cyclodextrin (β-CD) via the heterobifunctional polyethyleneglycol (PEG) linker NHS-PEG-MAL, yielding Lf conjugated β-cyclodextrin (Lf-CD). UV-vis, FTIR, NMR and transmission electron microscopy (TEM) techniques clearly demonstrated the successful synthesis of Lf-CD nanoparticles with the average diameter of 92.9 ± 16.5 nm. Using near-infrared fluorescent dye IR-775 chloride (IR) as a model compound of poorly water-soluble drugs, IR-loaded Lf-CD nanoparticles (Lf-CD/IR) were successfully prepared with a high entrapment efficiency of 98.1 ± 4.8%. Biodistribution and pharmacokinetics of Lf-CD/IR were evaluated in KM mice after intravenous administration. The results of tissue distribution studies revealed that Lf-CD/IR treatment showed greatly improved BBB transport efficiency. In addition, AUC0-2h of IR in brain after Lf-CD/IR treatment was seven fold higher compared with that of IR treatment without Lf-CD nano-carriers, demonstrating that the introduction of Lf-CD drug-delivery system positively resulted in a higher AUC located in brain tissue. These results provide evidence that Lf-CD nanoparticles could be exploited as a potential brain-targeting drug delivery system for hydrophobic drugs and diagnostic reagents which normally fail to pass through the BBB., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Chitosan (CS) grafted with β-cyclodextrin (CD-g-CS) nanoparticles as a new carrier for poorly water-soluble drugs has been developed. The CD-g-CS polymer is readily synthesized from chitosan and mono-6-deoxy-6-(p-toluenesulfonyl)-β-cyclodextrin. Three different degrees of substitution (DS) of β-cyclodextrin (β-CD) on CD-g-CS (9.6, 14.0 and 20.0%) are designed and evaluated by controlling the mole ratio of β-CD to chitosan. Then CD-g-CS nanoparticles are prepared by an ionic gelation method, with the controlled size of 202.0-589.0 nm. Stable colloidal dispersion of the nanoparticles has been formed with the zeta potential of +23.0 to +43.0 mV. In vitro stability test indicates that CD-g-CS nanoparticles are more stable in phosphate-buffered saline compared with CS nanoparticles. Finally, the poorly water-soluble drug, ketoprofen (KTP), is used as a model drug to evaluate the efficiency of the new drug delivery carrier. It is found that the encapsulation efficiency of KTP in the nanoparticles with 20% DS of CD is as high as 1.36-fold than that of CS nanoparticles. Moreover, notably KTP is released from the nanoparticles in a controlled-release manner and is pH-responsive on DS of CD. In summary, these results suggest that the CD-g-CS nanoparticles, as a general promising drug delivery system, can be used as a potential biodegradable nano-drug delivery system for controlled release of poorly water-soluble drugs with pH-responsive capability., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Neurotoxicity was investigated in nano-SiO2-treated cultured PC12 cells, an in vitro neuronal cell model, in order to define a relatively safe dose range for its application. The following were observed in the present study: (1) A dose-dependent increase in the level of reactive oxygen species (ROS) with a corresponding decrease in the level of glutathione (R2=0.965) suggesting 20- and 50-nm SiO2-induced free radical generation and glutathione depletion. (2) A dose- and time-dependent decrease in cell viability that was associated with elevation of ROS level, especially after 24-h nano-SiO2 exposure (R2=0.965), suggesting the role of oxidative stress on nano-SiO2 induced cell death. (3) An increase in the level of thiobarbituric-acid reactive species that correlated reversely with cell viability of the PC12 cells treated with nano-SiO2 (R2=0.945) suggesting nano-SiO2-induced membrane damage caused by lipid peroxidation. (4) A dose-dependent increase in sub-G1 population in SiO2-exposed cells along with cell shrinkage and nuclear condensation from morphological examination suggesting nano-SiO2-induced cell apoptosis. Furthermore, nano-SiO2 exposure diminished the ability of neurite extension in response to nerve growth factor in treated PC12 cells. In summary, SiO2 nanoparticle exposure resulted in dose-dependent neurotoxicity in cultured PC12 cells that was probably associated with oxidative stress and induced apoptosis., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Aims: In this article we report our recent developments in the field of electron paramagnetic resonance oximetry., Materials & Methods: Novel synthesized ferrocenyl nitroxide radicals (FcN)-1-6 were evaluated to determine their electron paramagnetic resonance oxygen responsiveness and reduction resistance. The 3-ferrocenyl-N-(oxyl-2,2,6,6-tetramethylpiperidin-4-yl) butanamide radical (FcN-6), with outstanding electron paramagnetic resonance oxygen sensitivity, was encapsulated in Pluronic F-127 polymeric nanoparticles., Results: The nanoparticles exhibited good oxygen sensitivity, long-term stability of responsiveness, targeting to lung, liver and tumor, and low toxicity., Conclusion: These features make this novel nanoparticle especially valuable for mapping O₂ concentrations in the body and monitoring the oxygen level inside tissues.

Nanoparticles such as nano-SiO(2) are increasingly used in food, cosmetics, diagnosis, imaging and drug delivery. However, toxicological data of nano-SiO(2) on hepatic cells in vitro and their detailed molecular mechanisms still remain unclear. In order to assess toxicity of nano-SiO(2), L-02 cells were exposed to 0.2, 0.4 and 0.6 mg/ml of SiO(2) colloids (21, 48 and 86 nm) for 12, 24, 36 and 48h. Lactate dehydrogenase released from damaged cells were quantified, cellular ultrastructural organization was observed, and the levels of reactive oxygen species (ROS), lipid peroxidation and glutathione were measured. Apoptosis induced by 21 nm SiO(2) was characterized by annexin V-FITC/PI staining and DNA ladder assay. Furthermore, apoptosis related proteins such as p53, Bax and Bcl-2 were analyzed by using western blot analysis. Our data indicated that nano-SiO(2) caused cytotoxicity in size, dose and time dependent manners. Oxidative stress and apoptosis were induced by exposure to 21 nm SiO(2). Moreover, the expression of p53 and Bax was increased in time and dose dependent patterns, whereas the expression of Bcl-2 was not significantly changed. In conclusion, ROS-mediated oxidative stress, the activation of p53 and up-regulation of Bax/Bcl-2 ratio are involved in mechanistic pathways of 21 nm SiO(2) induced apoptosis in L-02 cells., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO(2) nanoparticles at dosage levels between 20 and 100 microg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD(50)) of 24h exposure was 80.2+/-6.4 and 140.3+/-8.6 microg/ml for 20 and 50 nm SiO(2) nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO(2) nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO(2) nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO(2) nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO(2) nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.

Individualized immunotherapy has attracted great attention due to its high specificity, effectiveness, and safety. We used an exogenous antigen to label tumor cells with MHC I molecules, which allowed neoantigen-specific T cells to recognize and kill tumor cells. A neoantigen vaccine alone cannot achieve complete tumor clearance due to a tumor immunosuppressive microenvironment. The LightOn system was developed to effectively eliminate tumor cells through the spatiotemporally controllable expression of diphtheria toxin A fragment, leading to antigen release in the tumor region. These antigens stimulated and enhanced immunological function and thus, recruited neoantigen-specific T cells to infiltrate tumor tissue. Using the nanoparticle delivery system, neoantigens produced higher delivery efficiency to lymph nodes and improved tumor targeting ability for tumor cell labelling. Good tumor inhibition and prolonged survival were achieved, while eliciting a strong immune response. The combination of a spatiotemporally controllable transgene system with tumor neoantigen labeling has great potential for tumor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

When an acute myocardial infarction (AMI) occurs, myoglobin (Mb) is the biomarker whose concentration firstly increases, and the high sensitive detection of Mb is critical for early diagnosis of AMI. Herein, a sandwich-type electrochemical aptasensor for the sensitive detection of Mb was constructed by using Pt@Cu 1.33 OCo 0.83 O as the signal marker. On one hand, nano-flower-like Cu 1.33 OCo 0.83 O was synthesized by hydrothermal method and Pt nanoparticles (Pt NPs) were loaded on its surface. Pt@Cu 1.33 OCo 0.83 O could immobilize aptamer 2 (Apt2) successfully by the Pt–S bond. And because of the synergistic effect between Pt and bimetallic oxide, Pt@Cu 1.33 OCo 0.83 O had an excellent catalytic effect on the signal source of hydrogen peroxide (H 2 O 2) to amplify the current signal, which enhance the sensitivity of the aptasensor. On the other hand, the screen-printed gold electrode (SPGE) was used as the sensing base, which had good conductivity and ensured the immobilization of aptamer 1 (Apt1). The quantitative detection of Mb was achieved by specific recognition between Mb and Apt1, Apt2. As a result, the constructed electrochemical aptasensor had a good linear range (1–1500 ng/mL) with a low detection limit (LOD) of 0.128 ng/mL (S/N = 3), and a high sensitivity of 29.47 μA dec−1. The aptasensor also realized the detection of Mb in human serum samples with good accuracy, and the results were consistent with the hospital's biochemical indicators, which demonstrated the potential application of the prepared sensor in the clinical detection of Mb. [Display omitted] • A sandwich-type electrochemical aptasensor was fabricated based on Pt@Cu 1.33 OCo 0.83 O. • The label Pt@Cu 1.33 OCo 0.83 O made the aptasensor reach a high sensitivity of 29.47 μA dec−1. • The constructed aptasensor can detect Mb in human serum samples and is consistent with hospital's biochemical indicators. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel strategy for the simultaneous detection of Cd(II) and Pb(II) with high sensitivity is proposed. • Nitrogen-doped carbon-encapsulates Bi nanoparticles were synthesized. • Nitrogen-doped carbon nanosheets can help to improve electronic conductivity. • Uniformly dispersed Bi nanoparticles provide abundant active sites. Cadmium (Cd) and lead (Pb) are two of the most toxic heavy metals, which cause serious pollution to the environment. It is of great significance to develop electrochemical sensing platforms that can be used for the efficient and simultaneous detection of Cd(II) and Pb(II). Herein, bismuth nanoparticles encapsulated in nitrogen-doped carbon nanosheets (Bi@NC) were successfully synthesized. An electrochemical sensor based on Bi@NC was proposed for the high-performance determination of trace Cd(II) and Pb(II). Encapsulated and uniformly distributed Bi nanoparticles with abundant active sites form alloys with Cd(II) and Pb(II), and the conductive nitrogen-doped carbon nanosheet accelerates the electron transport rate, thus the electrochemical signals of Cd(II) and Pb(II) are significantly amplified. Under optimized conditions, Cd(II) and Pb(II) can be simultaneously detected in concentrations ranging from 1 to 150 μg L−1, with sensitivity of 0.48 μA μg−1 L and 0.36 μA μg−1 L, respectively. Meanwhile, the sensor possesses the outstanding advantages of ultra-high sensitivity, excellent selectivity, and storage stability, being able to serve as an electrochemical platform for Cd(II) and Pb(II) sensing in fruit and river water. [ABSTRACT FROM AUTHOR]

In this work, we proposed a new and facile strategy for the high-performance colorimetric detection of Ag + based on the tunable peroxidase-like activity of Pd nanoparticles (NPs) mediated by histidine (His). Bare Pd NPs possess intrinsic catalytic ability to trigger the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue TMBox in the presence of H 2 O 2 . After being decorated by His, the formed His-Pd nanozyme exhibits significantly improved mimetic activity due to its favorable physicochemical characteristics including smaller size, interactions between Pd and His, and better hydrophilicity, and such that an enhanced TMB color reaction is observed. When Ag + exists, it is able to despoil the His modifier from the His-Pd surface via the specific interaction between Ag + and His, resulting in the bald Pd again with weak activity. With this principle, highly sensitive determination of Ag + in a linear scope of 30–300 nM was achieved with a limit of detection down to 4.7 nM. In addition, the colorimetric sensor based on the tunable enzymatic activity of nanosized Pd adjusted by His could provide excellent selectivity for Ag + sensing against common interferents. Reliability of the strategy for practical detection of Ag + was also demonstrated. [ABSTRACT FROM AUTHOR]

Adenosine, as an endogenous nucleoside modulator, plays an important role in heart rate regulation, neurotransmission, and control of the respiratory system and thus it is significantly important to realize its sensitive detection. Herein, a highly sensitive electrochemical aptasensor for adenosine detection was proposed by using multi-walled carbon nanotubes (MWCNTs) as support matrix loading PtCu nanoparticles (PtCu-MWCNTs) to amplify signal. On one hand, disposable screen-printing gold electrodes (SPGEs) were used as superb sensing base to ensure the stable connection of aptamers 1 (ssDNA1). On the other hand, the PtCu-MWCNTs complex was synthesized through a one-pot method, which not only can precisely control the proportion of metal mass in the product but also exhibited superior electrocatalytic activity towards H 2 O 2. The recognition reactions were achieved by stepwise incubation of ssDNA1, ssDNA2-PtCu-MWCNTs (denoted as ssDNA2-label), and adenosine on the SPGEs. As a result, the constructed electrochemical aptasensor exhibited a wide linear range from 10 nM to 1.0 μM with a low detection limit of 1.0 nM (S/N = 3) for adenosine detection. The aptasensor also successfully realized the adenosine detection in human serum samples, which means that the proposed aptasensor holds a potential application in point-of-care detection. [Display omitted] • PtCu-MWCNTs composite can be easily synthesized through a one-pot method. • The metal mass ratio of PtCu-MWCNTs can be precisely control by manipulating the ratio of reactants. • PtCu-MWCNTs complex, showed excellent electrocatalytic performance towards H 2 O 2 as a signal amplification label. • The proposed electrochemical aptasensor had realized adenosine detection in the human serum. [ABSTRACT FROM AUTHOR]

Arsenic(III) is a highly toxic pollutant in the environment, and the development of nanomaterials with high electrochemical activity for As(III) detection is a research focus at present. Herein, an electrochemical sensing platform based on polyaniline nanofibers embedded with Ag@SiO 2 nanoparticles (Ag@SiO 2 /PANI NFs) was successfully constructed for trace As(III) determination. Owing to an in-situ chemical oxidation polymerization strategy, the polyaniline nanofibers loaded with Ag@SiO 2 core-shell nanoparticles blossomed into the dendritic three-dimensional network. The unique structure with a huge specific surface area greatly enhanced the adsorption efficiency of As(III). Combined with the outstanding conductivity of polyaniline and the electrocatalytic ability of uniformly dispersed AgNPs, the stripping current signal of As(III) was further amplified. Based on the optimized conditions, the sensitivity of 0.83 μA μg−1 L was obtained in the linear range of 0.1 ~ 100 μg L−1 with a low detection limit of 0.013 μg L−1. And the selectivity, reproducibility, and long-term stability of this sensor were excellent. Additionally, satisfactory results were achieved by the recovery experiment of real samples, and the accuracy of this method was verified by comparison with ICP-MS. The above results demonstrated the promising application of the as-fabricated sensor in As(III) detection. • An in-situ polymerization strategy for conductive polymers loaded with inorganic materials was proposed. • Ag@SiO 2 core-shell structure helped to avoid agglomeration of Ag nanoparticles. • Ag@SiO 2 /PANI NFs with dendritic network structure contributed to electrosorption of As(III). • The amplification of As(III) stripping current signal was achieved by modification of electrode. • The sensor showed high sensitivity and low detection limit for As(III) determination in the environment. [ABSTRACT FROM AUTHOR]

In the present work, a high-performance enzyme-based electrochemical sensor for the detection of superoxide anion radical (O 2 ●− ) is reported. Firstly, we employed a facile approach to synthesize PtPd nanoparticles (PtPd NPs) on chemically reduced graphene oxide (RGO) coated with polydopamine (PDA). The prepared PtPd-PDARGO composite was well characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectra, X-ray diffraction, X-ray photoelectron spectroscopy and electrochemical methods. Then the assembled composite was used as a desired electrochemcial interface for superoxide dismutase (SOD) immobilization. Owing to the PDA layer as well as the synergistic effect of PtPd NPs, the fabricated SOD/PtPd-PDARGO sensor exhibited an outstanding sensitivity of 909.7 μA mM −1 cm −2 upon O 2 ●− in a linear range from 0.016 mM to 0.24 mM ( R 2 =0.992), with a low detection limit of 2 μM (S/N=3) and excellent selectivity, good reproducibility as well as favorable long-term stability. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the study is to develop a new formulation for clinically used anti-cancer agent tacrolimus (FK506) to minimize the severe side effects. Toward this end, a new formulation method has been developed by complexation of FK506 with an hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) using ultrasonic means. The resulting complex displays dramatically enhanced solubility of FK506. Then bovine serum albumin (BSA) nanoparticles were prepared directly from the preformed FK506/DM-β-CD inclusion complex by the desolvation-chemical crosslinking method, with the size of 148.4–262.9nm. Stable colloidal dispersions of the nanoparticles were formed with zeta potentials of the range of −24.9 to −38.4mV. The entrapment efficiency of FK506 was increased as high as 1.57-fold. Moreover, notably FK506 was released from the nanoparticles in a sustained manner. As demonstrated, pharmacokinetic studies reveal that, as compared with FK506-loaded BSA nanoparticles, the FK506/DM-β-CD inclusion complex-loaded BSA nanoparticles have significant increase at T max, t 1/2, MRT and decrease at C max. In summary, these results suggest that the drug/DM-β-CD inclusion complex-loaded BSA nanoparticles display significantly improved delivery efficiency for poorly soluble FK506 or its derivatives. [Copyright &y& Elsevier]

Abstract: Nanoparticles such as nano-SiO2 are increasingly used in food, cosmetics, diagnosis, imaging and drug delivery. However, toxicological data of nano-SiO2 on hepatic cells in vitro and their detailed molecular mechanisms still remain unclear. In order to assess toxicity of nano-SiO2, L-02 cells were exposed to 0.2, 0.4 and 0.6mg/ml of SiO2 colloids (21, 48 and 86nm) for 12, 24, 36 and 48h. Lactate dehydrogenase released from damaged cells were quantified, cellular ultrastructural organization was observed, and the levels of reactive oxygen species (ROS), lipid peroxidation and glutathione were measured. Apoptosis induced by 21nm SiO2 was characterized by annexin V-FITC/PI staining and DNA ladder assay. Furthermore, apoptosis related proteins such as p53, Bax and Bcl-2 were analyzed by using western blot analysis. Our data indicated that nano-SiO2 caused cytotoxicity in size, dose and time dependent manners. Oxidative stress and apoptosis were induced by exposure to 21nm SiO2. Moreover, the expression of p53 and Bax was increased in time and dose dependent patterns, whereas the expression of Bcl-2 was not significantly changed. In conclusion, ROS-mediated oxidative stress, the activation of p53 and up-regulation of Bax/Bcl-2 ratio are involved in mechanistic pathways of 21nm SiO2 induced apoptosis in L-02 cells. [Copyright &y& Elsevier]

Abstract: In the present study, toxicities of silica nanoparticles with sizes of 21 and 48nm were assessed in myocardial H9c2(2-1) cells using the methylthiazolyldiphenyl-tetrazolium bromide reduction and lactate dehydrogenase assays. Cell injuries were characterized by morphological changes using hematoxylin and eosin staining. Reactive oxygen species, malondialdehyde and glutathione were measured to evaluate the levels of oxidative stress. To elucidate mechanisms, cell cycle distributions and the expressions of p53, p21 and Bax were also analyzed. Results showed that silica nanoparticles produced cytotoxicities in size, dose (0.1–1.6mg/ml) and time (12, 24, 36 and 48h exposure) dependent manners. Moreover, the particles caused oxidative stress, induced G1 phase arrest and upregulated levels of p53 and p21. Taken together, these data suggested that cell injuries were triggered by the generation of oxidative stress; p53 and p21 mediated G1 phase arrest is a potential mechanistic pathway of silica nanoparticles induced damage in H9c2(2-1) cells. [Copyright &y& Elsevier]

The detection of circulating tumor DNA (ctDNA) has increasingly received a great deal of attention considering its significance in cancer diagnosis. And the signal amplification plays an important role in the development of sensitive ctDNA biosensors. Herein, the nanocomposites (denoted as HAC-AuPt), integrating from high-active carbon (HAC) and AuPt alloy nanoparticles, were synthesized and subsequently used as a signal amplification label to fabricate a sandwich-type ctDNA electrochemical biosensor. Characterizations demonstrated that HAC presents uniform size distribution and AuPt alloy nanoparticles were successfully loaded on HAC. The current response could be amplified to a great extent by the resultant HAC-AuPt due to its excellent electrochemical property. The nanocomposites were further bounded with DNA signal probes (SPs) via Au-S or Pt-S assembly to form SPs-label. After the capture probes (CPs) were immobilized on the electrode surface, the target DNA (tDNA) and SPs-label were stepwise incubated on the CPs-modified electrode, thus forming a sandwich-type structure. By monitoring the catalytic signal of HAC-AuPt towards the reduction process of H 2 O 2 , this biosensor provided a wide linear range of 10−8 mol/L - 10−16 mol/L with a low detection limit of 3.6 × 10−17 mol/L (S/N = 3) for the detection of the tDNA. Furthermore, obvious differences in response signals among different DNAs were observed benefitting from the excellent selectivity of the biosensor. Besides, the long-term stability, reproducibility, and recovery rate were proved to be outstanding. These results indicate that the established biosensor holds a potential application in the clinical diagnosis of ctDNA. [Display omitted] • A sandwich-type ctDNA electrochemical biosensor was designed based on HAC-AuPt. • The HAC-AuPt contains high-active sites of N, graphitized-C, Co-Nx, and AuPt alloy. • The current signal could be amplified largely by the synthesized HAC-AuPt. • The biosensor exhibits satisfying sensitivity and high selectivity for ctDNA detection. [ABSTRACT FROM AUTHOR]

Here we presented a new facile strategy to fabricate ultrathin two-dimensional (2D) metal oxide nanosheets, by using polydopamine-coated graphene (rGO@PDA) as a template under simply wet-chemical conditions. Based on the strategy, graphene-like CeO 2 –TiO 2 mesoporous nanosheet (MNS-CeO 2 -TiO 2) was prepared and was loaded with dispersive Ag nanoparticles (AgNPs) to obtain effective electrocatalysts (denoted as Ag/MNS-CeO 2 -TiO 2) for electrochemical detection of superoxide anion (O 2 •−). Characterizations demonstrated that MNS-CeO 2 -TiO 2 exhibited ultrathin thickness, larger specific surface area, and pore volume in comparison with its bulk counterpart. The above properties of MNS-CeO 2 -TiO 2 shorten electron transmission distance, promotes mass transfer, and is conducive to the dispersion of post-modified AgNPs. Therefore, the recommended Ag/MNS-CeO 2 -TiO 2 sensors (denoted as Ag/MNS-CeO 2 -TiO 2 /SPCE) exhibited satisfactory properties, including the sensitivity of 737.1 μA cm−2 mM−1, the detection limit of 0.0879 μM (S/N = 3), and good selectivity. Meanwhile, the sensors also successfully realized in the online monitoring of O 2 •− released from HepG2 cells, meaning the prepared sensors had practical application potential towards the analysis of O 2 •− in biological samples. • A novel facile strategy for preparing ultrathin 2D metal oxide nanosheets was presented. • Based on above strategy, Ag/MNS-CeO 2 -TiO 2 were prepared with controllable morphology. • The superoxide anion (O 2 •−) electrochemical sensor was successfully fabricated with Ag/MNS-CeO 2 -TiO 2. [ABSTRACT FROM AUTHOR]

• A simple modification method on carbon fiber microelectrodes (CFME) via in-situ reduction of AuAg bimetallic nanoparticles by polydopamine was proposed, and it offered a universal strategy to decorate novel metals onto microelectrode for different application in the future. • The bimetal synergistic effect enabled AuAg bimetallic decorated electrodes exhibited higher electrocatalytic activity (compared with Au and Ag monometallic decorated electrodes), showing an obvious enhancement toward H 2 O 2 sensing. • With a low detection limit (0.1 μM), the prepared 2Au1Ag-PDA/CFME was capable of detecting H 2 O 2 released from HepG2 living cells, indicating a potential usage of the fabricated electrode for H 2 O 2 detection in cancer cells. In this work, a facile in-situ reduction method was developed for the modification of carbon fiber microelectrode (CFME) to build novel electrochemical sensors for the detection of H 2 O 2. The polydopamine (PDA) was employed as the surface modification material for one-step decoration of AuAg bimetallic nanoparticles through in-situ reduction on the surface of PDA/CFME. Compared to Au-PDA/CFME and Ag-PDA/CFME, 2Au1Ag-PDA/CFME (immersed PDA/CFME in AgNO 3 for 1 h, HAuCl 4 •4H 2 O for 2 h in order) exhibited higher electrocatalytic activity toward H 2 O 2 sensing due to bimetal synergism. Under the optimal condition, the 2Au1Ag-PDA/CFME appeared a wide linear range of 0 μM - 55 μM (R2 = 0.990), 55 μM – 2775 μM (R2 = 0.991) with high sensitivity (12966 μA mM−1cm−2, 0–55 μM; 2534 μA mM−1 cm−2, 55–2775 μM), and low detection limit (0.12 μM). Furthermore, good selectivity and repeatability of 2Au1Ag-PDA/CFME favored its applications in biological samples, especially in cellular level. The detection of H 2 O 2 released from HepG2 living cells was realized by applying 2Au1Ag-PDA/CFME, indicating a potential usage of the fabricated electrode for H 2 O 2 detection in cancer cells. In addition, the above simple in-situ reduction method based on PDA's adhesion and reducibility offered a universal strategy to decorate noble metals onto microelectrode for different application in the future. Image, graphical abstract [ABSTRACT FROM AUTHOR]