Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H 2 O 2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO 2 -SiO 2 @HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo. Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO 2 , and coated with dopamine. Then, MnO 2 was modified on the SiO 2 . Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups. Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H 2 O 2 in the GOD-mediated reaction. The generated sufficient H 2 O 2 was catalyzed by MnO 2 and HGNs-Fc@Ce6 to produce O 2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect. Conclusion:The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.
The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anti-cancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy.
Objective: The aim of this research was to utilize bioinformatics techniques to explore the molecular mechanisms at the gene level that contribute to asthma, with the objective of discovering new treatment strategies and potential targets for addressing the condition. Methods: The Series Matrix File data files of GSE43696 and GSE67940 were downloaded from the NCBI GEO public database, including expression profile data of 212 patients. Differential gene expression was functionally annotated using clusterProfiler to evaluate relevant functional categories with GO and KEGG. A gene co-expression network was constructed using MEGENA, and feature importance was evaluated by random forest algorithm. Fluorescent quantitative PCR was employed to validate the expression of essential genes, and the variations in KEGG signaling pathways among the groups with high and low expression were examined through GSEA. Asthma targeted therapeutic drugs were predicted using The Connectivity Map. Finally, single-cell sequencing data were annotated and analyzed using the Seurat and celldex packages. Results: This study screened 267 differentially expressed genes between asthma patients and healthy controls from the GSE43696 dataset and further analyzed them using pathway analysis and multi-scale embedded gene co-expression network analysis, ultimately selecting 12 genes as the candidate gene set for random forest analysis. Based on this, five key genes were selected using random forest algorithm, and their expression was validated in the external dataset GSE67940. The expression of C1orf64 and C7orf26 genes was found to be different between the two groups of patients, and these two genes were found to be associated with immune regulatory factors, chemokines, and cell receptors. The mRNA expression levels of C1orf64 and C7orf26 were consistent with the results of the screening by PCR. Further analysis showed that C1orf64 and C7orf26 were enriched in ABC transporters, cell cycle, cell adhesion molecules, and Notch signaling pathways, and were related to other genes related to asthma. Finally, by classifying the differentially expressed genes using the Connectivity Map, potential clues were provided for finding candidate drugs for asthma treatment. Conclusion: This study combined bioinformatics methods to identify key genes and pathways for asthma. C1orf64 and C7orf26 genes may be the core genes in the pathogenesis of asthma in asthma patients compared to healthy controls, providing potential targets for asthma treatment. These results also suggest the potential application of drug prediction analysis using CMap and single-cell sequencing analysis in understanding the molecular mechanisms of asthma.
A highly sensitive electrochemical biosensor was manufactured with triple synergistic catalysis to detect hydrogen peroxide (H 2 O 2 ). In this study, a highly sensitive biosensor based on Prussian blue-chitosan/graphene-hemin nanomaterial/platinum and palladium nanoparticles (PB-CS/HGNs/Pt&Pd biosensor) was fabricated for the detection of H 2 O 2 . The materials described above were modified on the electrode surface and applied to catalyze the breakdown of hydrogen peroxide. The current response of the biosensor presented a linear relationship with H 2 O 2 concentration from 6 × 10 −2 to 20 μM (R 2 = 0.9766) and with the logarithm of H 2 O 2 concentration from 20 to 9×10 3 μM (R 2 = 0.9782), the low detection limit of 25 nM was obtained at the signal/noise (S/N) ratio of 3. Besides, the biosensor showed an outstanding anti-interference ability and acceptable reproducibility. PB-CS/HGNs/Pt&Pd electrodes are effective in measuring H 2 O 2 from living tumor cells, which implies that the biosensor has the potential to assess reactive oxygen species in various living tumor cells.
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