Tumor microenvironment (TME)-mediated cancer therapy, such as chemodynamic therapy (CDT) based on Fenton reaction, has attracted extensive attention in recent years. However, efficient Fenton reactions usually require stringent reaction conditions (low pH value and sufficient H 2 O 2 ). Therefore, there is an urgent need to improve the efficiency of Fenton reaction within the tumor for enhanced CDT in cancer treatment. Herein, Cu 2 Se hollow nanocubes (HNCs) are successfully prepared via an anion exchange method using Cu 2 O nanocubes (NCs) as the template. This method is also successfully used to synthesize Cu 2 S or CuSSe HNCs with the similar structure. By tuning the reaction time in the process of transforming Cu 2 O NCs into Cu 2 Se HNCs, Cu 2 Se HNCs with optimized performances in high NIR II photothermal conversion efficiency (50.89%) and good Fenton-like properties are obtained. After surface coating, PEGylated Cu 2 Se HNCs show good water dispersibility and biocompatibility. Importantly, in vitro and in vivo experiments demonstrate the significant synergistic effect of combining photothermal therapy (PTT) and CDT based on PEG-Cu 2 Se HNCs, achieving greatly enhanced efficacy than that obtained by PTT or CDT alone. Moreover, such PEG-Cu 2 Se HNCs appear to be rather safe for treated animals without noticeable long-term toxicity.
Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis.
Multifunctional biodegradable inorganic theranostic nano-agents are of great interest to the field of nanomedicine. Upon lipid modification, VS nanosheets could be converted into ultra-small VS nanodots encapsulated inside polyethylene glycol (PEG) modified lipid micelles. Owing to paramagnetism, high near-infrared (NIR) absorbance, and chelator-free Tc labeling of VS , such VS @lipid-PEG nanoparticles could be used for T1-weighted magnetic resonance (MR), photoacoustic (PA),and single photon emission computed tomography (SPECT) tri-modal imaging guided photothermal ablation of tumors. Importantly, along with the gradual degradation of VS , our VS @lipid-PEG nanoparticles exhibit effective body excretion without appreciable toxicity. The unique advantages of VS nanostructures with highly integrated functionalities and biodegradable behaviors mean they are promising for applications in cancer theranostics.
Sonodynamic therapy (SDT), a noninvasive and highly penetrating tumor therapy, which employs ultrasound and sonosensitizers, has attracted extensive attention because of its ability to treat deep tumors. However, many current sonosensitizers have drawbacks in phototoxicity and limited sonodynamic effect. Herein, as a novel kind of sonosensitizer, iron-doped vanadium disulfide nanosheets (Fe-VS2 NSs) are constructed by a high-temperature organic-solution method and further modified with polyethylene glycol (PEG). With Fe doping, the sonodynamic effect of Fe-VS2 NSs is greatly enhanced, owing to the prolonged electron–hole recombination time. Simultaneously, such Fe-VS2-PEG NSs as a good Fenton agent can be utilized for chemodynamic therapy (CDT) by using the endogenous H2O2 in the tumor microenvironment (TME). Moreover, the multivalent Fe and V elements in the Fe-VS2 NSs can consume glutathione to amplify the reactive oxygen species-induced oxidative stress by SDT and CDT. Utilizing the strong near-infrared optical absorbance and enhanced magnetic resonance (MR) contrast by Fe-VS2 NSs, photoacoustic/MR biomodal imaging reveals a high accumulation of Fe-VS2-PEG NSs in the tumor. The great tumor suppression effect is then achieved by the in vivo combined CDT&SDT treatment. Importantly, most of the injected Fe-VS2-PEG NSs can be gradually decomposed and excreted from the mice, making them as safe sonosensitizers for cancer treatment. Our work highlights a new type of biodegradable sonosensitizer with the ability of regulating TME for applications in cancer theranostics.
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