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Smart Plasmonic Nanozyme Enhances Combined Chemo-Photothermal Cancer Therapy and Reveals Tryptophan Metabolic Apoptotic Pathway
摘要： The tumor microenvironment regulation is considered as an intelligent strategy for cancer therapeutics, but the related metabolic pathways of cell apoptosis still remains a great challenge. Herein, by applying multifunctional carbon dot-decorated Ag/Au bimetallic nanoshells (CDs-Ag/Au NSs, CAANSs) nanoprobes as smart plasmonic nanozymes for combined chemo-photothermal cancer therapy, we achieved a high efficiency in cancer cell therapy and revealed a tryptophan metabolic apoptotic pathway. In addition to high photothermal conversion efficiency, the CAANSs can act as a smart nanozyme to catalyze intracellular H2O2 to the cytotoxic reactive oxygen species (ROS) of superoxide anion (·O2-) in response to mild acidic cancerous cell microenvironment to damage cellular DNA. More importantly, the tryptophan metabolic pathway during the combined chemo-photothermal therapy has been revealed that the tryptophan participates in oxidative stress process, which can be decomposed to produce H2O2 and further formed into superoxide anion to kill cells under the catalytic nanomedicine process. The current work provides an effective platform for cancer therapeutics and is promising for cancer-related molecular biology studies.
关键词： Tryptophan Metabolic Apoptotic Pathway,Smart Plasmonic Nanozyme,Tumor Microenvironment,Chemo-Photothermal Cancer Therapy,Reactive Oxygen Species
更新于2025-09-11 14:15:04
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A novel pro-apoptotic role of zinc octacarboxyphthalocyanine in melanoma me45 cancer cell's photodynamic therapy (PDT)
摘要： Zn-based phthalocyanine acts as drug or photosensitizer in photodynamic therapy (PDT) for the treatment of cancer cells. The activated zinc octacarboxyphthalocyanine (ZnPcOC) reacts with oxygen, to generate reactive oxygen species for the damage of melanoma cancer cells, Me45. This in vitro study aimed at investigating the cytotoxic effects of different concentrations of ZnPcOC activated with a diode laser (λ=685 nm) on Me45, and normal human fibroblast cells, NHDF. To perform this study 104 cells/ml were seeded in 96-well plates and allowed to attach overnight, after which cells were treated with different concentrations of ZnPcOC (10, 20 and 30 μM). After 4 h, cells were irradiated with a constant light dose of 2.5; 4.5 and 7.5 J/cm2. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT viability assay. Data indicated that high concentrations of ZnPcOC (30 μM) in its inactive state are not cytotoxic to the melanoma cancer cells and normal fibroblasts. Moreover, the results showed that photoactivated ZnPcOC (30 μM) was able to reduce the cell viability of melanoma and fibroblast to about 50%, respectively. At this photosensitizing concentration the efficacy the treatment light dose of 2.5; 4.5 and 7.5 J/cm2 was evaluated against Me45 cells. ZnPcOC at a concentration of 30 μM activated with a light dose of 2.5; 4.5 and 7.5 J/cm2 was the most efficient for the killing of melanoma cancer cells. Melanoma cancer cells after PDT with a photosensitizing concentration of 30 μM ZnPcOC and a treatment light dose of 2.5; 4.5 and 7.5 J/cm2 showed certain pro-apoptotic characteristics, such as direct inducer (early apoptosis) and long-term inducer, also (late apoptosis). This concludes that low concentrations of ZnPcOC, activated with the appropriate light dose, can be used to induce cell death in melanoma cells via ROS-induces apoptosis pathway, what was confirmed with cytometric ROS measurements. Our in vitro study showed that ZnPcOC mediated photodynamic therapy is an effective treatment option for melanoma Me45 cancer cells. 30 μM of ZnPcOC with the treatment light dose of 2.5 J/cm2 from a LED diode laser source, with a wavelength of 685 nm, was adequate to destroy melanoma cancer cells via ROS-induced apoptosis pathway, with low killing effects on healthy NHDF normal fibroblasts.
关键词： photosensitizers,zinc octacarboxyphthalocyanine (ZnPcOC),UV-Vis spectra,pro-apoptotic activity,photodynamic therapy (PDT),reactive oxygen species (ROS),melanoma Me45 cancer cells
更新于2025-09-09 09:28:46
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Selection and Quantification of Objects in Microscopic Images: from Multi-Criteria to Multi-Threshold Analysis
摘要： Due to the increased number of applications of both microscopic imaging and image analysis including biomedical studies, the design of specialized algorithms and tools to facilitate quantitative assessment of objects in the image content is of urgent need. Recently, a number of approaches ranging from object counting by machine learning methods to statistical image analysis have been suggested and successfully implemented to resolve the cell quantification problem. Here, we revisit the above problem considering samples where objects presented in the same images have to be explicitly distinguished and quantified without involving any dedicated experimental setting like differential fluorescent staining. We consider several possible classification criteria and show explicitly how their combination in a single algorithm can be used to improve results in complex images where single criteria-based rules inevitably fail. Finally, we suggest a possible approach for the analysis of non-homogeneous images based on combining object selection results for different threshold values thus enhancing the algorithm from multi-criteria to multi-threshold analysis. To demonstrate the performance of the suggested solutions, we show several prominent examples of complex structures ranging from images containing both live and apoptotic cells as well as containing mixtures of globular and fibrous forms of heat-shock protein IbpA.
关键词： Microscopy,Image analysis,Apoptotic,Cell sub-populations,Fibers
更新于2025-09-04 15:30:14