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Colorimetric qualitative and sensitive quantitative detection of Salmonella Typhimurium (S. Typhimurium) holds significant importance for ensuring food safety and preventing foodborne illnesses. In the study, an ultra-high catalytic activity and biocompatible nickel-platinum nanoparticle (NiPt NP) nanozyme is successful synthesized to prepare a NLISA strategy for the detection of S. Typhimurium. The synthesized NiPt NPs exhibit high oxidase-like catalytic efficiency, with a Michaelis constant (Km) of 0.493 mM, similar to that of natural horseradish peroxidase (HRP). The maximal reaction velocity (Vmax) was determined to be 1.97 × 10-7 M·s-1 exhibiting a 1.97-fold higher than that of the HRP (1.0 × 10-7 M·s-1). Meanwhile, the antibody employed in this NiPt NPs-based NLISA exhibits exceptional capture efficacy, generating a stable immune complex with S. Typhimurium. The NiPt NPs-based NLISA demonstrates sensitivity, specificity, convenience, and cost-efficiency for the detection of S. Typhimurium. Under optimal conditions, this NiPt NPs-based NLISA demonstrates a quantitative range of 103â¼106 cfu/mL with a detection limit as low as 103 cfu/mL. A single-blind experimental testing detects different concentrations of S. Typhimurium spiked skim milk, indicating the application potential of the proposed NLISA in real samples. In all, this research provides novel insights into the synthesis of nanozymes with excellent catalytic activity and their applications in S. Typhimurium biosensing.
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Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy.
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Antineoplásicos , Glutationa , Nanopartículas , Fotoquimioterapia , Pró-Fármacos , Espécies Reativas de Oxigênio , Glutationa/metabolismo , Glutationa/química , Nanopartículas/química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Camundongos , Ensaios de Seleção de Medicamentos Antitumorais , Tamanho da Partícula , Peróxido de Hidrogênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Propriedades de Superfície , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Microambiente Tumoral/efeitos dos fármacos , IndolquinonasRESUMO
The high glutathione (GSH) level of the tumor microenvironment severely affects the efficacy of photodynamic therapy (PDT). The current GSH depletion strategies have difficulty meeting the dual needs of security and efficiency. In this study, we report a photosensitizer Chlorin e6 (Ce6) and hypoxia-activated prodrug tirapazamine (TPZ) coloaded cross-linked multifunctional polymersome (TPZ/Ce6@SSPS) with GSH-triggered continuous GSH depletion for enhanced photodynamic therapy and hypoxia-activated chemotherapy. At tumor sites, the disulfide bonds of TPZ/Ce6@SSPS react with GSH to realize decross-linking for on-demand drug release. Meanwhile, the generated highly reactive quinone methide (QM) can further deplete GSH. This continuous GSH depletion will amplify tumor oxidative stress, enhancing the PDT effect of Ce6. Aggravated tumor hypoxia induced by PDT activates the prodrug TPZ, resulting in an enhanced combination of PDT and hypoxia-activated chemotherapy. Both in vitro and in vivo results demonstrate the efficient GSH depletion and potent antitumor activities by TPZ/Ce6@SSPS. This work provides a strategy for the design of a continuous GSH depletion platform, which holds great promise for enhanced combination tumor therapy.
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Clorofilídeos , Glutationa , Fotoquimioterapia , Fármacos Fotossensibilizantes , Pró-Fármacos , Tirapazamina , Glutationa/metabolismo , Fotoquimioterapia/métodos , Tirapazamina/farmacologia , Animais , Camundongos , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pró-Fármacos/farmacologia , Porfirinas/farmacologia , Porfirinas/administração & dosagem , Porfirinas/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacosRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.
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Antibacterianos , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Fármacos Fotossensibilizantes , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico por imagem , Camundongos , Testes de Sensibilidade Microbiana , HumanosRESUMO
Wild edible mushrooms are a huge source to discover bioactive natural products. In this work, one new polyprenylphenol derivative, termed 2-geranylgeranyl-1,4-benzenediol 1-O-acetate (1), together with eight known compounds (2-9) were isolated from wild edible mushroom Suillus luteus. The structure of new compound was elucidated by high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance data. The structures of known compounds were elucidated by comparison of their nuclear magnetic resonance data with literature data. Compounds 1-7 exhibited significant 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity with IC50 values ranging from 1.55 ± 0.29 to 19.89 ± 2.28 µM. In addition, compounds 1-7 also showed tyrosinase inhibitory activity with IC50 values ranging from 21.97 ± 3.74 to 66.26 ± 6.85 µM.
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Agaricales , Basidiomycota , Agaricales/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Espectrometria de Massas por Ionização por Electrospray , Estrutura Molecular , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
Edible and medicinal mushrooms are extensively cultivated and commercially consumed around the world. However, green mold disease (causal agent, Trichoderma spp.) has resulted in severe crop losses on mushroom farms worldwide in recent years and has become an obstacle to the development of the Ganoderma industry in China. In this study, a new species and a new fungal pathogen on Ganoderma sichuanense fruitbodies were identified based on the morphological characteristics and phylogenetic analysis of two genes, the translation elongation factor 1-α (TEF1) and the second-largest subunit of RNA polymerase II (RPB2) genes. The new species, Trichoderma ganodermatigerum sp. nov., belongs to the Harzianum clade, and the new fungal pathogen was identified as Trichoderma koningiopsis. Furthermore, in order to better understand the interaction between Trichoderma and mushrooms, as well as the potential biocontrol value of pathogenic Trichoderma, we summarized the Trichoderma species and their mushroom hosts as best as possible, and the phylogenetic relationships within mushroom pathogenic Trichoderma species were discussed.
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Paxillus, a type of ectomycorrhizal fungi distributed widely in the world, is also an essential category for researching bioactive substances and pharmacological functions. We discovered fruitbodies of Paxillusinvolutus covered in a layer of white mycelium in 2020. Cladobotryumverticillatum, a pathogenic fungus related to cobweb disease, was isolated and identified based on morphological and phylogenetic features. Koch's postulates were used to confirm the pathogenicity. The host range test revealed that C.verticillatum could cause disease in all examined mushrooms except Ganodermasichuanense. To our knowledge, C.verticillatum is a new record species in China and a new pathogen on Paxillusinvolutus.
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Reactive oxygen species (ROS)-related therapeutic approaches are developed as a promising modality for cancer treatment because the aberrant increase of intracellular ROS level can cause cell death due to nonspecific oxidation damage to key cellular biomolecules. However, the most widely considered strategy, photodynamic therapy (PDT), suffers from critical limitations such as limited tissue-penetration depth, high oxygen dependence, and phototoxicity. Non-photo-induced ROS generation strategies, which are defined as Xdynamic therapies (X = sono, radio, microwave, chemo, thermo, and electro), show good potential to overcome the drawbacks of PDT. Herein, recent advances in the development of Xdynamic therapies, including the design of systems, the working mechanisms, and examples of cancer therapy application, are introduced. Furthermore, the approaches to enhance treatment efficiency of Xdynamic therapy are highlighted. Finally, the perspectives and challenges of these strategies are also discussed.
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Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes , Espécies Reativas de OxigênioRESUMO
An ideal nanotheranostic agent should be able to achieve efficient tumor accumulation, retention, and fast elimination after its theranostic functions exhausts. However, there is an irreconcilable contradiction on optimum sizes for effective tumor retention and fast elimination. Herein, a programmed size-changeable nanotheranostic agent based on polyprodrug-modified iron oxide nanoparticles (IONPs) and aggregation-induced emission photosensitizer is developed for enhanced magnetic resonance imaging (MRI)-guided chemo/photodynamic combination therapy. The nano-sized theranostic agents with an initial diameter of about 90 nm can accumulate in tumor tissue through passive targeting. In the acidic tumor microenvironment, large aggregates of IONPs are formed, realizing enhanced tumor retention and MR signal enhancement. Under the guidance of MRI, light irradiation is applied to the tumor site for triggering the generation of reactive oxygen species and drug release. Moreover, after chemo/photodynamic combination therapy, the large-sized aggregates are re-dispersed into small-sized IONPs for fast elimination, reducing the risk of toxicity caused by long-term retention. Therefore, this study provides a promising size-changeable strategy for the development of nanotheranostic agents.
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Fotoquimioterapia , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Doxorrubicina , Humanos , NanopartículasRESUMO
Chemotherapy serves as one of the most effective approaches in numerous tumor treatments but also suffers from the limitations of low bioavailability and adverse side effects due to premature drug leakage. Therefore, it is crucial to realize accurate on-demand drug release for promoting the application of chemotherapeutic agents. To achieve this, stimuli-responsive nanomedicines that can be activated by delicately designed cascade reactions have been developed in recent years. In general, the nanomedicines are triggered by an internal or external stimulus, generating an intermediate stimulus at tumor site, which can intensify the differences between tumor and normal tissues; the drug release process is then further activated by the intermediate stimulus. In this review, the latest progress made in cascade reactions-driven drug-release modes, based on the intermediate stimuli of heat, hypoxia, and reactive oxygen species, is systematically summarized. The perspectives and challenges of cascade strategy for drug delivery are also discussed.
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Vascular endothelial growth factor (VEGF) is the key regulator in neovascular lesions. The anti-VEGF injection is a major way to relieve retinal neovascularization and treat these diseases. However, current anti-VEGF therapeutics show significant drawbacks. The reason is the inability to effectively control its therapeutic effect. Therefore, how to controllably inhibit the VEGF target is a key point for preventing angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed for the precise regulation of pathologic neovascularization. This system is composed of a light-controlled regulatory component and transcription inhibition component. They work together to controllably and effectively inhibit the target gene's VEGF. The opto-CRISPR nanosystem achieved precise regulation according to individual differences, whereby the expression and interaction of gene was activated by light. The following representative model laser-induced choroid neovascularization and oxygen-induced retinopathy were taken as examples to verify the effect of this nanosystem. The results showed that the opto-CRISPR nanosystem was more efficacious in the light control group (NV area effectively reduced by 41.54%) than in the dark control group without light treatment. This strategy for the CRISPR-optogenetic gene nanosystem led to the development of approaches for treating severe eye diseases. Besides, any target gene of interest can be designed by merely replacing the guide RNA sequences in this system, which provided a method for light-controlled gene transcriptional repression.
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Materiais Biocompatíveis/farmacologia , Neovascularização de Coroide/tratamento farmacológico , Lasers , Optogenética , Animais , Materiais Biocompatíveis/química , Células Cultivadas , Neovascularização de Coroide/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/efeitos dos fármacos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Feminino , Humanos , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
To date, many methods have been developed for inducing tumor cell death, such as using chemical drugs and radiation. However, all of them have a common problem, a lack of mechanisms for precisely regulating the death of tumor cells. It often leads to nonspecific death and systemic side effects. Therefore, the efficacy and further application of these traditional methods are limited. In this paper, a logic AND-gated sonogene nanosystem was designed for precisely regulating the apoptosis of tumor cells. The running of this system required two essential parts, MscL I92L channel protein and ultrasound. Ultrasound could open the MscL I92L protein channel which when expressed on cells triggers the influx and outflux of small molecules through the channel. When the channel is kept open for a long time, Ca2+ influx becomes excessive which in turn activates the Ca2+ apoptosis pathway of cells. The expression of MscL I92L protein and the applying of ultrasound constituted the logic AND gate which could implement the precise regulation to apoptosis. This strategy would help reduce nonspecific triggers and side effects. In this system, cationic nanoliposomes were prepared as the carrier for effectively delivering MscL I92L plasmids to tumor cells in vivo. We investigated the apoptosis-promoting effect of this system in different tumor cell lines (HeLa, B16, and 4T1). The results demonstrated that the apoptosis rate was highest in the B16 cell line (the early apoptosis rate was 11.9% and the late apoptosis rate was 59.1%) when the cells were subjected to consistent ultrasound (6 MHz, 15 W) for 30 min. This logic AND-gated sonogene nanosystem is expected to provide a new strategy and development direction for tumor therapy.
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Antineoplásicos/uso terapêutico , Apoptose/fisiologia , DNA/uso terapêutico , Canais Iônicos/química , Neoplasias/terapia , Ondas Ultrassônicas , Animais , Linhagem Celular Tumoral , DNA/genética , Portadores de Fármacos/química , Feminino , Técnicas de Transferência de Genes , Humanos , Canais Iônicos/genética , Lipossomos/química , Lógica , Camundongos , Plasmídeos/genética , Plasmídeos/uso terapêuticoRESUMO
Cortinarius is an important ectomycorrhizal genus that forms a symbiotic relationship with certain trees, shrubs and herbs. Recently, we began studying Cortinarius in China and here we describe three new species of Cortinarius subg. Telamonia based on morphological and ecological characteristics, together with phylogenetic analyses. Cortinarius laccariphyllus sp. nov. (section Colymbadini) is associated with broadleaf trees, with strongly hygrophanous basidiomata, special Laccaria-like lamellae and white and extremely sparse universal veil. Cortinarius neotorvus sp. nov. (section Telamonia) is associated with broadleaf trees and is easily confused with C. torvus, but can be distinguished by the colour of the fresh basidiomes and the stipe usually somewhat tapering towards the base. Cortinarius subfuscoperonatus sp. nov. (section Fuscoperonati) is associated with coniferous trees, with subglobose to broadly ellipsoid spores and is closely related to C. fuscoperonatus. A key to the new species and similar species in sections Colymbadini, Telamonia and Fuscoperonati is provided.
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Photodynamic therapy (PDT) is an oxygen-dependent, non-invasive cancer treatment. The hypoxia in the tumor environment limits the therapeutic effects of PDT. The combined delivery of photosensitizers and hypoxic prodrugs is expected to improve the efficacy of tumor treatment. In this paper, an erythrocyte and tumor cell membrane camouflage nanocarrier co-loaded with a photosensitizer (indocyanine green) and a hypoxic prodrug (tirapazamine) were used to combine PDT with chemotherapy. The system achieved less macrophage clearance through erythrocyte membranes and tumor-targeted tumor cell membranes, thereby inducing cell death and increasing tumor environment hypoxia by NIR irradiation of photosensitizers. Furthermore, the hypoxic environment activated TPZ to kill more tumor cells. In vivo results showed that the tumor inhibition rate of the drug-loaded nanoparticles increased from 34% to 64% after membrane modification. Moreover, the tumor inhibition rate of the photodynamic treatment group alone was only 47%, and the tumor inhibition rate after the combination was 1.3 times that of photodynamic therapy alone. Our platform is expected to contribute to the further application of cancer combination therapy.