ABSTRACT
Co-pyrolysis of biomass with phosphogypsum (PG) presents an effective strategy for facilitating the recycling of PG resources. However, it is crucial to note the environmental threats arising from the presence of Pb, Cr, Ni, and F in PG. This study investigated the effect of immobilization and transformation of four elements during co-pyrolysis with biomass and its components. The co-pyrolysis experiments were carried out in a tube furnace with a mixture of PG and corn stover (CS), cellulose (C), lignin (L), glucose (G). Co-pyrolysis occurred at varying temperatures (600 °C, 700 °C, 800 °C, and 900 °C) and different addition ratios (10%, 15%, and 20%). The results indicated that an increase in co-pyrolysis temperature was more conducive to the immobilization and transformation of harmful elements in PG, demonstrating significant efficacy in controlling F. Additionally, the addition of biomass components exerts a significant impact on inhibiting product toxicity, with small molecules such as glucose playing a prominent role in this process. The mechanism underlying the control of harmful elements during co-pyrolysis of PG and biomass was characterized by three main aspects. Firstly, biomass components have the potential to melt-encapsulate the harmful elements in PG, leading to precipitation. Secondly, the pyrolysis gas produced during the co-pyrolysis process contributes to the formation of a rich pore structure in the product. Finally, this process aids in transforming hazardous substances into less harmful forms and stabilizing these elements. The findings of this study are instrumental in optimizing the biomass and PG blend to mitigate the environmental impact of their co-pyrolysis products.
Subject(s)
Biomass , Calcium Sulfate , Chromium , Fluorine , Lead , Nickel , Nickel/chemistry , Chromium/chemistry , Lead/chemistry , Fluorine/chemistry , Calcium Sulfate/chemistry , Phosphorus/chemistry , Zea maysABSTRACT
Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L-arginine-loaded selenium-coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)-induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.
Subject(s)
Myocardial Reperfusion Injury , Rats , Animals , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Nitric Oxide/metabolism , Reactive Oxygen Species/therapeutic use , Gold , Arginine/metabolism , Mitochondria/metabolismABSTRACT
[This corrects the article DOI: 10.7150/thno.34755.].
ABSTRACT
Background: Singlet oxygen (1O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne. After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne. With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1O2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.
Subject(s)
Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Tumor Microenvironment , Light , Neoplasms/drug therapy , Hypoxia/drug therapy , Cell Line, TumorABSTRACT
Sonosensitizers that can increase the concentration of reactive oxygen species (ROS) within a tumor microenvironment is a high priority for sonodynamic therapy (SDT). In this study, a functionalized, smart nanosonosensitizer based on Au-RuO2 nanoparticles (NPs) and selenium nanoparticles (Se NPs) that were electrostatically self-assembled onto the surface of Listeria innocua (LI) was used to create Bac@ARS. Au NPs provided the core in which RuO2 was deposited to form Au-RuO2 NPs. Additionally, the underlying properties of the Au NPs and Se NPs were used to optimize the sonosensitivity performance. Compared with pristine RuO2 NPs, Bac@ARS exhibits highly efficient ROS-producing activity. Furthermore, Bac@ARS remodeled the hypoxic tumor microenvironment, enabling overproduction of ROS. Importantly, Bac@ARS exploits the natural tropism of LI to selectively accumulate in tumors, which improved the treatment precision at hypoxic tumor sites after sonodynamic activation. However, the activity of LI was greatly reduced after ultrasound (US) irradiation, ensuring the biosafety of Bac@ARS. Bac@ARS was also used to monitor tumors, in real time, using photoacoustic imaging of the gold-based nanoparticles. Therefore, Bac@ARS is a promising microbial sonosensitizer providing a new platform for the optimization of sonosensitizers for tumor treatment. STATEMENT OF SIGNIFICANCE: A bio-nano-sonosensitizer was designed using a Au nanoparticle (NP) core modified with RuO2 NPs. The Au-RuO2 NPs together with Se-NPs are attached via electrostatic adsorption to a live bacterium Listeria innocua (LI), creating Bac@ARS. The role of the NPs was to optimize the sonosensitivity performance at the target tumor site. Bac@ARS reshaped the tumor microenvironment and overcame tumor hypoxia leading to ROS overproduction. This activated a potent ICD-mediated cellular immunity and anti-tumor activity. Importantly, Bac@ARS exploited the natural tropism of LI to selectively accumulate in tumors, resulting in more precise delivery of the therapeutic effect while exhibiting reduced effects on healthy tissues.
Subject(s)
Metal Nanoparticles , Nanoparticles , Neoplasms , Ultrasonic Therapy , Humans , Reactive Oxygen Species , Gold/pharmacology , Cell Line, Tumor , Metal Nanoparticles/therapeutic use , Neoplasms/therapy , Neoplasms/pathology , Nanoparticles/therapeutic use , Tumor MicroenvironmentABSTRACT
Mitochondrial dysfunction and oxidative damage represent important pathological mechanisms of myocardial ischemia-reperfusion injury (MI/RI). Searching for potential antioxidant agents to attenuate MI/RI is of great significance in clinic. Herein, gold-selenium core-shell nanostructures (AS-I/S NCs) with good near-infrared (NIR)-II photoacoustic imaging were designed for MI/RI treatment. The AS-I/S NCs after ischemic myocardium-targeted peptide (IMTP) and mitochondrial-targeted antioxidant peptide SS31 modification achieved cardiomyocytes-targeted cellular uptake and enhanced antioxidant ability and significantly inhibited oxygen-glucose deprivation-recovery (OGD/R)-induced cardiotoxicity of H9c2 cells by inhibiting the depletion of mitochondrial membrane potential (MMP) and restoring ATP synthase activity. Furthermore, the AS-I/S NCs after SS31 modification achieved mitochondria-targeted inhibition of reactive oxygen species (ROS) and subsequently attenuated oxidative damage in OGD/R-treated H9c2 cells by inhibition of apoptosis and oxidative damage, regulation of MAPKs and PI3K/AKT pathways. The in vivo AS-I/S NCs administration dramatically improved myocardial functions and angiogenesis and inhibited myocardial fibrosis through inhibiting myocardial apoptosis and oxidative damage in MI/RI of rats. Importantly, the AS-I/S NCs showed good safety and biocompatibility in vivo. Therefore, our findings validated the rational design that mitochondria-targeted selenium-gold nanocomposites could attenuate MI/RI of rats by inhibiting ROS-mediated oxidative damage and regulating MAPKs and PI3K/AKT pathways, which could be a potential therapy for the MI/RI treatment.
Subject(s)
Myocardial Reperfusion Injury , Nanocomposites , Photoacoustic Techniques , Selenium , Rats , Animals , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Selenium/pharmacology , Selenium/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Antioxidants/metabolism , Gold/pharmacology , Gold/metabolism , Myocardial Reperfusion Injury/diagnostic imaging , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Myocytes, Cardiac/metabolism , Apoptosis , Oxidative StressABSTRACT
Fenugreek seeds (Trigonella foenum-graecum L.), one kind of traditional Chinese medicine, are reported to be of great potential as a new alternative in terms of their bioactive components. In our present study, an ultrasonic-assisted method was applied in the extraction of antioxidative components from fenugreek seeds. Four factors: ethanol concentration, liquid-solid ratio, sonication time, and sonication power were selected and multiple responses were studied using the response surface methodology (RSM). The effects of factors along with the correlation between all responses (flavonoids content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, OH- assay) were studied. The regression model indicated that all four factors are of significant effect on all responses. The model predicted that the ethanol concentration of 72%, solvent-to-material ratio of 35 ml/g, ultrasonic time of 41 min, and 500 W of power would provide a flavonoid yield of 9.10 mg/g, DPPH clearance of 80.33%, and OH- clearance of 24.28%, respectively. The confirmation test showed the closeness of the predicted results with those of experimental values. And AB-8 resin was successfully used to purify the fenuellus hulusi seed extract, and the flavonoid concentration of 78.14% was obtained. Six flavonoids (Swertisin, Puerarin apioside, Jasminoside B, Astragalin, Apigenin-7-O-beta-D-glucoside, and Apiin) were successfully identified by the liquid chromatography-mass spectrometry (LC-MS) analysis.
ABSTRACT
Methicillin-resistant Staphylococcus (MRS) is a multi-drug resistant bacteria that pose a serious threat to human health. Antibacterial nanomaterials are becoming a promising antibiotic substitute or antibiotic adjuvants. In this work, selenium nanowires were modified with nanosilver (Ag NPs) with antibacterial activity and [Ru(bpy)2dppz]2+ with fluorescent labeling of DNA (SRA), and the antibacterial activity, antibacterial mechanism and biological toxicity of SRA synergistic antibiotics were studied. In vitro, antibacterial results show that SRA (12 µg/mL) improves the antibacterial activity of various antibiotics against resistant bacteria and significantly slows the development of bacterial resistance to antibiotics. Studies on antibacterial mechanisms have shown that SRA synergistic antibiotics destroy drug-resistant bacteria through a combination of physical (physical damage) and chemical pathways (destruction of biofilm, membrane depolarization, cell membrane destruction, adenosine triphosphate consumption and reactive oxygen species production). Transcriptomics analysis found that SRA affects bacterial activity by affecting bacterial biosynthesis, ATP synthesis and biofilm formation. Furthermore, SRA synergistic antibiotics can accelerate wound healing of bacterial infection by reducing the inflammatory response. The toxicity evaluation results show that SRA has extremely low cellular and in vivo toxicity. SRA has the potential of clinical application as multiple antibiotic adjuvants to deal with resistant bacterial infections.
Subject(s)
Bacterial Infections , Methicillin-Resistant Staphylococcus aureus , Nanowires , Selenium , Anti-Bacterial Agents/pharmacology , Bacteria , Drug Resistance, Multiple, Bacterial , Humans , Selenium/pharmacologyABSTRACT
Unsupervised deep learning methods have shown great success in jointly estimating camera pose and depth from monocular videos. However, previous methods mostly ignore the importance of multi-scale information, which is crucial for pose estimation and depth estimation, especially when the motion pattern is changed. This article proposes an unsupervised framework for monocular visual odometry (VO) that can model multi-scale information. The proposed method utilizes densely linked atrous convolutions to increase the receptive field size without losing image information, and adopts a non-local self-attention mechanism to effectively model the long-range dependency. Both of them can model objects of different scales in the image, thereby improving the accuracy of VO, especially in rotating scenes. Extensive experiments on the KITTI dataset have shown that our approach is competitive with other state-of-the-art unsupervised learning-based monocular methods and is comparable to supervised or model-based methods. In particular, we have achieved state-of-the-art results on rotation estimation.
ABSTRACT
Bacterial infections can cause many human diseases, which are closely related to people's health. Nowadays, antibiotics are mainly used to treat bacterial infections, but the widespread use of antibiotics can also lead to bacterial resistance. Therefore, effective treatment of bacterial infections is an urgent problem to be solved. In this article, a multifunctional therapeutic material with antibacterial properties was designed and synthesized. First, the porous media material ZIF-8 was synthesized, and applied to load hesperidin. When the load is completed, a layer of hyaluronic acid (HA) is uniformly wrapped on surface of the material. Such materials have high stability and high drug-carrying capacity, and can be slowly released in vivo. The HA coated on surface can also promote penetration of active ingredients into cells and give full play to antibacterial ability. Results of in vitro and in vivo antibacterial tests show that synergy between the materials enhances antibacterial activity which is related to dose. The material achieves high-efficiency antibacterial effects by increasing the permeability of cell membranes and destroying the integrity of bacteria. At same time, the material does not show obvious side effects. Therefore, the material seems to be a promising antibacterial agent with good biocompatibility and strong antibacterial activity.
Subject(s)
Bacterial Infections , Metal-Organic Frameworks , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Excipients , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Hyaluronic Acid/pharmacology , Metal-Organic Frameworks/therapeutic use , SterilizationABSTRACT
Photodynamic antibacterial therapy employs nanocomposites as an alternative to traditional antibiotics for the treatment of bacterial infections. However, many of these antibacterial materials are less effective towards bacteria than traditional drugs, either due to poor specificity or antibacterial activity. This can result in needless and excessive drug use in treatments. This paper describes a multifunctional drug delivery nanoparticle (MDD-NP), Sph-Ru-MMT@PZ, based on the nanostructured-form of [Ru(bpy)2dppz] (PF6)2 (Sph-Ru), which has adhesive properties towards its microbial targets as well as surface-anchoring photosensitizer effects. The design and construction of MDD-NP is based on the adhesive properties of the outer layers of montmorillonite (MMT), which allows Sph-Ru-MMT@PZ to successfully reach its bacterial target; the outer layer of the E. coli. In addition, under 670 nm red irradiation therapy (R-IT), the surface-anchoring properties use the photosensitizer phthalocyanine zinc (PZ) to destroy the bacteria by producing reactive oxygen species (ROS) which causes cell lysis of E. coli. More importantly, Sph-Ru-MMT@PZ has no fluorescence response to live E. coli with intact cell membranes but selectively stained and demonstrated fluorescence during membrane damage of early-stage cells as well as exposure of nuclear materials at late-stage of cell lysis. Sph-Ru-MMT@PZ showed beneficial and synergistic anti-infective effects in vivo by inhibiting the E. coli infection-induced inflammatory response and eventually promoting wound healing in mice. This new strategy for high precision antibacterial therapy towards specific targets, provides an exciting opportunity for the application of multifunctional nanocomposites towards microbial infections.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Adhesion/drug effects , Nanoparticles/chemistry , Photosensitizing Agents/chemistry , Pyridines/chemistry , Ruthenium/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/pathology , Coordination Complexes/chemistry , Disease Models, Animal , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Hemolysis/drug effects , Indoles/chemistry , Indoles/pharmacology , Isoindoles , Mice , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Reactive Oxygen Species/metabolism , Surface Properties , Wound Healing/drug effectsABSTRACT
BACKGROUND: Nano-Fenton reactors as novel strategy to selectively convert hydrogen peroxide (H2O2) into active hydroxyl radicals in tumor microenvironment for cancer therapy had attracted much attention. However, side effects and low efficiency remain the main drawbacks for cancer precise therapy. RESULTS: Here, ruthenium-loaded palmitoyl ascorbate (PA)-modified mesoporous silica (Ru@SiO2-PA) was successfully fabricated and characterized. The results indicated that Ru@SiO2-PA under pH6.0 environment displayed enhanced growth inhibition against human cancer cells than that of pH7.4, which indicated the super selectivity between cancer cells and normal cells. Ru@SiO2-PA also induced enhanced cancer cells apoptosis, followed by caspase-3 activation and cytochrome-c release. Mechanism investigation revealed that Ru@SiO2-PA caused enhanced generation of superoxide anion, which subsequently triggered DNA damage and dysfunction of MAPKs and PI3K/AKT pathways. Moreover, Ru@SiO2-PA effectively inhibited tumor spheroids and tumor xenografts growth in vivo by induction of apoptosis. The real-time imaging by monitoring Ru fluorescence in vitro and in vivo revealed that Ru@SiO2-PA mainly accumulated in cell nucleus and tumor xenografts. Importantly, Ru@SiO2-PA showed no side effects in vivo, predicting the safety and potential application in clinic. CONCLUSIONS: Our findings validated the rational design that Ru@SiO2-PA can act as novel tumor microenvironment-response nano-Fenton reactors for cancer precise therapy.
Subject(s)
Ruthenium/chemistry , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Tumor Microenvironment/drug effects , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , DNA Damage/drug effects , Humans , Hydrogen Peroxide , Mice , Mice, Nude , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Phosphatidylinositol 3-Kinases , Xenograft Model Antitumor AssaysABSTRACT
Co-delivery of H2O2-generating agent and catalyst via a nano-Fenton reactor to the tumor acidic microenvironment for amplified tumor oxidation therapy has been widely studied. However, high side effects and low efficiency remain the limitations of the design and development of this process. Herein, a new nano-Fenton reactor in which mesoporous silica is integrated with Fe3O4 and palmitoyl ascorbate (Fe3O4@SiO2-PA) was designed, with the product exhibiting good dispersion, stability, uniformity and consistent spectral characteristics. The results show that Fe3O4@mSiO2-PA successfully enters cancer cells, significantly inhibits HeLa cells and 3D tumor spheroid growth in vitro via the induction of apoptosis. Meanwhile, Fe3O4@mSiO2-PA administration in vivo markedly suppresses HeLa tumor xenografts growth via the induction of apoptosis, followed by caspase-3 activation and cytochrome C release. Further investigation revealed that Fe3O4@mSiO2-PA causes enhanced production of reactive oxygen species (ROS), which subsequently triggers DNA damage and causes dysfunction of the MAPK and PI3K/AKT pathways. Importantly, Fe3O4@mSiO2-PA shows few side effects and good biocompatibility in vivo. Taken together, these results suggest that Fe3O4@mSiO2-PA inhibits HeLa cell growth in vitro and in vivo by triggering enhanced oxidative damage and regulating multiple signal pathways. Our findings validate the rational design that mesoporous silica integrated with Fe3O4 and palmitoyl ascorbate can act as a new nano-Fenton reactor for amplified tumor oxidation therapy.
Subject(s)
Hydrogen Peroxide , Silicon Dioxide , Animals , Ascorbic Acid/analogs & derivatives , Ferric Compounds , Ferrosoferric Oxide , HeLa Cells , Humans , Nanoparticles , Phosphatidylinositol 3-Kinases , Xenograft Model Antitumor AssaysABSTRACT
With the emergence of vehicular Internet-of-Things (IoT) applications, it is a significant challenge for vehicular IoT systems to obtain higher throughput in vehicle-to-cloud multipath transmission. Network Coding (NC) has been recognized as a promising paradigm for improving vehicular wireless network throughput by reducing packet loss in transmission. However, existing researches on NC do not consider the influence of the rapid quality change of wireless links on NC schemes, which poses a great challenge to dynamically adjust the coding rate according to the variation of link quality in vehicle-to-cloud multipath transmission in order to avoid consuming unnecessary bandwidth resources and to increase network throughput. Therefore, we propose an Adaptive Network Coding (ANC) scheme brought by the novel integration of the Hidden Markov Model (HMM) into the NC scheme to efficiently adjust the coding rate according to the estimated packet loss rate (PLR). The ANC scheme conquers the rapid change of wireless link quality to obtain the utmost throughput and reduce the packet loss in transmission. In terms of the throughput performance, the simulations and real experiment results show that the ANC scheme outperforms state-of-the-art NC schemes for vehicular wireless multipath transmission in vehicular IoT systems.
ABSTRACT
This study proposes the synthesis of a type of anticancer nanoparticle, aptamers and Au nanoparticle (Apt-Au)-modified Morin pH-sensitive liposome (MSL), which exhibits targeting properties. Tumors are difficult to cure because their microenvironment varies from that of normal tissue; its pH is lower than that of normal tissue, which generally impedes the effectiveness of drugs. Thus, pH-responsive drugs have attracted extensive attention. Gold nanoparticles (AuNPs) show potential as drug carriers because of their small size, good biocompatibility, easy surface modification, and strong cell penetration. Apt-Au@MSL exhibits excellent monodispersity and tumor-targeting properties and can be released in partly acidic environment via dialysis. We screened our model cancer cell by MTT assay and found that SGC-7901 cells can effectively suppress proliferation. In vivo results demonstrate that the administration of Apt-Au@MSL could inhibit tumor growth in xenograft mouse models. H&E staining and TUNEL assay further confirmed that Apt-Au@MSL can promote tumor apoptosis. Apt-Au@MSL may induce apoptosis by triggering overproduction of reactive oxygen species (ROS) and regulating multiple signal crosstalk. Both blood biochemistry tests and H&E staining suggested that these materials exhibit negligible acute toxicity and good biocompatibility in vivo. With its powerful function, Apt-Au@MSL can be used as a target-based anticancer material for future clinical cancer treatment.
ABSTRACT
Diseases caused by pathogenic bacilli pose an increasing threat to human health. A common feature of these bacteria is a complete cell wall; therefore, drugs that can penetrate this protective barrier could be used as a novel approach for treating these infections. Here we present a simple method for synthesizing a silica mesoporous material loaded with cadmium selenide (CdSe) and chlorogenic acid. Using UV-visible, fluorescence, and infrared imaging in combination with transmission electron microscopy, it was shown that CdSe and chlorogenic acid could be successfully embedded in the mesopores of silica nanoparticles (CSC NPs), and these NPs presented with a strong fluorescence, uniform size, and good dispersion. Additionally, the results of these analyses indicated that the fluorescence of the CSC NPs was localized within the cells of Escherichia coli and Bacillus subtilis, signifying that these NPs could breach the cell wall and enter the cells of these two bacilli. Additional assessments found that these CSC NPs inhibited the proliferation of the bacteria by disrupting the cell wall, and this was most likely due to the overproduction of reactive oxygen species induced by chlorogenic acid. Importantly, histopathology analysis indicated that the CSC NPs had limited side effects and high biocompatibility.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorogenic Acid/pharmacology , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Silicon Dioxide/pharmacology , Animals , Bacillus subtilis/drug effects , Bacillus subtilis/ultrastructure , Cadmium Compounds/toxicity , Chlorogenic Acid/toxicity , Escherichia coli/drug effects , Escherichia coli/ultrastructure , Male , Mice, Nude , Microbial Sensitivity Tests , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Porosity , Reference Standards , Selenium Compounds/toxicityABSTRACT
Photothermal therapy as novel strategy to convert near-infrared (NIR) light into heat for treatment cancers has attracted great attention and been widely studied. However, side effects and low efficiency remain the main challenge of precise cancer photothermal therapy. Methods: In this study, we have successfully fabricated and characterized the dual-targeted gold nanoprisms, whereby bare gold nanoprisms (Au NPR) were conjugated to a phenanthroline derivatives-functionalized tetraphenylethene (TPE) and further stabilized with target peptide aptamers via Au-S bonds (Au-Apt-TPE). Then, the remaining nitrogen atoms of the Au-Apt-TPE could effectively chelate with Zn2+ ions (Au-Apt-TPE@Zn) for monitoring early stage apoptotic cells. Results: The as-synthesized Au-Apt-TPE@Zn exhibited good monodispersity, size stability and consistent spectral characteristics. TPE synthesized here showed aggregation-induced emission (AIE) characteristics, and zinc conjunction (TPE@Zn) endowed Au-Apt-TPE@Zn with the cell membrane-targeted ability to selectively recognize the membranes of early stage apoptotic cells but not respond to healthy cells, which provided valuable diagnosis information on therapeutic efficacy. Au-Apt-TPE@Zn achieved specifically nuclear-targeted ability by surface decoration of AS1411 DNA aptamer. Au-Apt-TPE@Zn under NIR irradiation showed effective photothermal therapy against SGC-7901 human gastric carcinoma cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and regulating multiple signal crosstalk. In vivo studies revealed that Au-Apt-TPE@Zn under NIR irradiation showed deep penetration and dual-model imaging application (cancer-targeted fluorescence imaging and light-up photoacoustic imaging). Au-Apt-TPE@Zn under NIR irradiation also displayed strong photothermal therapy against gastric carcinoma xenograft growth in vivo by induction of apoptosis. Importantly, analysis of histopathology, hematotoxicity and immunocytotoxicity indicated that Au-Apt-TPE@Zn had less side effect and high biocompatibility. Conclusions: Our findings validated the design of using Au nanoprism with AIE materials and dual-targeted decoration could be an effective strategy in recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy.
Subject(s)
Apoptosis/drug effects , Gold/chemistry , Phototherapy , Stomach Neoplasms/therapy , Animals , Drug Delivery Systems , Gold/administration & dosage , Humans , Male , Metal Nanoparticles , Mice, Inbred BALB C , Reactive Oxygen Species/metabolism , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/metabolism , Stomach Neoplasms/physiopathology , Treatment Outcome , Xenograft Model Antitumor AssaysABSTRACT
A novel nanoparticle (Au-LTSL-GA.A) uses the thermosensitive liposome (LTSL) to encapsulate ganoderic acid A (GA.A), which successfully transforms the polarity of GA.A and has excellent water solubility. The multifunctional Au-LTSL-GA.A, a self-assembled thermal nanomaterial, was used in antibacterial and anticancer applications in combination with near-infrared (NIR) irradiation. The designed Au-LTSL-GA.A nanoparticle was used as a nano-photosensitizer to achieve synergistic photochemotherapy based on the phototherapy sensitization property of Au nanorods (NRs) and antitumour activity of GA.A. In the antibacterial experiments, the Au-LTSL-GA.A + NIR irradiation had a broad-spectrum antibacterial effect, exhibiting a strong antibacterial activity against drug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) compared with the raw GA.A and LTSL-GA.A. In the anticancer experiments, Au-LTSL-GA.A + NIR irradiation, which combined phototherapy sensitization property of Au NRs with antitumour activity of GA.A, exhibited high anticancer activity against MCF-7 cells. The IC50 value of Au-LTSL-GA.A + NIR irradiation (12.1 ± 1.3 µg/mL) was almost similar to cisplatin in MCF-7 cells. The evaluation of the potential in vivo toxicity of Au-LTSL-GA.A revealed no toxicity in mice. The results of this study suggest that Au-LTSL-GA.A has a wide range of potential industrial and clinical applications, such as in antibacterial treatment and cancer photochemotherapy.
Subject(s)
Anti-Bacterial Agents , Escherichia coli/growth & development , Gold , Metal Nanoparticles , Nanotubes/chemistry , Neoplasms/drug therapy , Photochemotherapy , Staphylococcus aureus/growth & development , Triterpenes , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Gold/chemistry , Gold/pharmacology , Humans , Liposomes , MCF-7 Cells , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Neoplasms/metabolism , Neoplasms/pathology , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Inositol requiring enzyme-1 (IRE1) is highly conserved from yeasts to humans. Upon endoplasmic reticulum (ER) stress, IRE1 activates X-box-binding protein 1 (XBP1) by unconventional splicing of XBP1 mRNA, which activates unfolded protein response (UPR) to restore ER homeostasis. In mice, IRE1α plays an essential role in extraembryonic tissues. However, its precise action during the early stage of development is unknown. In this study, the gain and loss-of-function analyses were used to investigate the function of Xenopus IRE1α (xIRE1α). The effects of xIRE1α during embryo development were detected with RT-PCR and whole mount in situ hybridization. ER stress was induced by tunicamycin. The apoptotic cells were measured by TUNNEL assays. Although both gain and loss of xIRE1α function had no significant effect on Xenopus embryogenesis, knockdown of xIRE1α could rescue tunicamycin-induced developmental defects and apoptosis. The finding indicates that xIRE1α is not required for embryogenesis but is required for tunicamycin-induced developmental defects and apoptosis in Xenopus laevis.