- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
A Multiparametric Evaluation of Quantum Dot Size and Surface-Grafted Peptide Density on Cellular Uptake and Cytotoxicity
摘要： Despite the progress in nanotechnology for biomedical applications, great efforts are still being employed in optimizing nanoparticle (NP) design parameters to improve functionality and minimize bionanotoxicity. In this study, we developed CdSe/CdS/ZnS core/shell/shell quantum dots (QDs) that are compact ligand-coated and surface-functionalized with an HIV-1-derived TAT cell-penetrating peptide (CPP) analog to improve both biocompatibility and cellular uptake. Multiparametric studies were performed in different mammalian and murine cell lines to compare the effects of varying QD size and number of surface CPPs on cellular uptake, viability, generation of reactive oxygen species, mitochondrial health, cell area, and autophagy. Our results showed that the number of cell-associated NPs and their respective toxicity are higher for the larger QDs. Meanwhile, increasing the number of surface CPPs also enhanced cellular uptake and induced cytotoxicity through the generation of mitoROS and autophagy. Thus, here we report the optimal size and surface CPP combinations for improved QD cellular uptake.
关键词： cellular uptake,mitochondrial health,cytotoxicity,biomedical applications,reactive oxygen species,nanotechnology,autophagy,quantum dots
更新于2025-09-19 17:13:59
-
Graphene Quantum Dots Induce Autophagy and Reveal Protection Against Hydrogen Peroxide-Induced Oxidative Stress Injury
摘要： As the zero-dimension nanomaterials, graphene quantum dots (GQDs) have excellent characteristics of graphene as well as photoluminescence (PL) features that ordinary graphene does not possess for its virtue of quantum confinement effect and boundary effect, and attract lots of researchers interested in the field of biomedical applications. In this work, we found GQDs can be internalized into SGC-7901 cells, and the labeled cells exhibited bright yellow fluorescence in the form of aggregated dots. Meanwhile, GQDs effectively mitigated the injury hydrogen peroxide (H2O2)-induced in SGC-7901 cells including cytotoxicity and apoptosis. While H2O2 exposure increased ROS and decreased mitochondrial membrane potential, it could be arrested by GQDs. Furthermore, GQDs showed protective effects against the reduction of the ratio of mitochondrial apoptosis-related proteins Bcl-2/ Bax in SGC-7901 cells. Our works revealed that GQDs had the antioxidant ability against oxidative stress, which meant they had the potential to be an antioxidants. Besides, GQDs increased the level of autophagy-related protein LC3-II and induced autophagic structure observed via TEM, and subsequent the results of LC3 turnover and p62 degradation demonstrated GQDs treatment led to the activation of autophagic flux. Ultimately, GQDs were found to affect autophagy through the mTOR signaling pathway.
关键词： graphene quantum dots,apoptosis,antioxidant,oxidative stress,autophagy
更新于2025-09-16 10:30:52
-
Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag <sub/>2</sub> S quantum dots
摘要： Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor.
关键词： lung cancer,EGFR,theranostic,Ag2S quantum dots,autophagy,targeted drug delivery,5-fluorouracil
更新于2025-09-16 10:30:52
-
Diverse autophagy and apoptosis in myeloid leukemia cells induced by 20(s)-GRh2 and blue LED irradiation
摘要： Autophagy is an important mechanism for cell death regulation. To improve the anticancer effect during the treatment of leukemia and promote the apoptosis of leukemic cells, it is important to define the relationship between autophagy and apoptosis. A key bioactive compound in traditional Chinese medicine, 20(s)-Ginsenoside (GRh2), demonstrated an advancement in leukemia treatment. Blue LED therapy (BL) is a physical treatment method that can induce leukemic cell death. In this study, we tested the effect of 20(s)-GRh2, BL, and their combination (BL–GRh2) on the activation of leukemic cell apoptosis and autophagy. Both treatments, whether used individually or simultaneously, induce apoptosis through the induction of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP) and regulated the expression of apoptosis-related genes and proteins. Furthermore, using western blotting to analyze the autophagy markers LC3B and P62, we detected the activation of autophagy. In cells treated with autophagy inhibitor 3-MA, both autophagy and apoptosis were inhibited, either by BL alone or by BL–GRh2. However, apoptosis in 20(s)-GRh2-treated cells was enhanced. In cells treated with apoptosis suppressor Z-VAD-FMK, autophagy was inhibited in the BL and BL–GRh2-treated cells, although it was enhanced in cells treated with 20(s)-GRh2 alone. Moreover, we observed a stronger induction of apoptosis by BL–GRh2 in myeloid leukemia cells. Our data indicate that autophagy induced by different factors can play diverse roles on the same cells. Our results also indicate that the combination of traditional Chinese medicine with physical therapy may be a new strategy for anti-cancer therapy.
关键词： 20(s)-GRh2,apoptosis,autophagy,leukemia,blue LED therapy
更新于2025-09-16 10:30:52
-
An Organelle-redirected Chameleon Sensor Enabled Live Cell Imaging of Mitochondrial DNA
摘要： Mitochondrial DNA (mtDNA) plays important roles in diverse physiological processes and myriad diseases. We herein report mtDNA imaging with a chameleon sensor containing a cationic rhodamine B (RB) entity for mitochondria targeting and a fluorogenic SYBR Green-I (SG) entity for DNA sensing. SG-RB selectively binds to mtDNA and gives green SG fluorescence in mitochondria of living cells but gives red RB fluorescence upon delivery of mitochondria into lysosomes in mitophagy. With the dual color imaging, mtDNA aggregation and elevated mitophagy were identified in HeLa cells stressed with anticancer doxorubicin. These results suggest the utility of organelle-redirected DNA sensors for live cell imaging of mtDNA involved in myriad pathological disorders.
关键词： Mitochondrial DNA,Fluorescence imaging,Color switch,Autophagy,Organelle targeting
更新于2025-09-11 14:15:04
-
Real-time monitoring of newly acidified organelles during autophagy enabled by reaction-based BODIPY dyes
摘要： Real-time monitoring of newly acidified organelles during autophagy in living cells is highly desirable for a better understanding of intracellular degradative processes. Herein, we describe a reaction-based boron dipyrromethene (BODIPY) dye containing strongly electron-withdrawing diethyl 2-cyanoacrylate groups at the α-positions. The probe exhibits intense red fluorescence in acidic organelles or the acidified cytosol while exhibiting negligible fluorescence in other regions of the cell. The underlying mechanism is a nucleophilic reaction at the central meso-carbon of the indacene core, resulting in the loss of π-conjugation entailed by dramatic spectroscopic changes of more than 200 nm between its colorless, non-fluorescent leuco-BODIPY form and its red and brightly emitting form. The reversible transformation between red fluorescent BODIPY and leuco-BODIPY along with negligible cytotoxicity qualifies such dyes for rapid and direct intracellular lysosome imaging and cytosolic acidosis detection simultaneously without any washing step, enabling the real-time monitoring of newly acidified organelles during autophagy.
关键词： cytosolic acidosis,fluorescence probe,autophagy,BODIPY,lysosome imaging
更新于2025-09-11 14:15:04
-
Selective castration-resistant prostate cancer photothermal ablation with CuS nanoplates
摘要： Objective: To explore new therapies for castration-resistant prostate cancer (CRPC) to improve patients’ quality of life and extend life. Materials and Methods: The synthesis, morphology analysis, phase analysis, spectral analysis and photothermal conversion test were referenced to our previous articles. Then NIR-light-driven CuS nanoplates to inhibit the growth of prostate cancer cells in vivo and in vitro was carried out. Transmission electron microscope, mCherry-LC3 syncytial virus labelling, acridine orange staining and autophagy protein were used to detect the autophagy caused by CuS nanoplates and chloroquine was used to inhibit the process of autophagy. Results: The CuS nanoplates prepared in this study feature low cytotoxicity, simple preparation and high photothermal conversion efficiency. Driven by 980nm near-infrared light, CuS nanoplates could inhibit the growth of prostate cancer cells in vivo and in vitro, while triggering the autophagy and cytoprotection of prostate cancer cells. Conclusions: CuS nanoplates are a kind of commendable photothermal therapy agent in CRPC treating. Autophagy inhibition enhances the photothermal efficiency of CuS nanoplates, which indicates favorable application prospects in the treatment of advanced prostate cancer.
关键词： CuS nanoplates,Autophagy,Photothermal therapy,CRPC
更新于2025-09-10 09:29:36
-
A Flow Cytometric Study of ER Stress and Autophagy
摘要： The mechanistic link between ER stress, autophagy, and resultant cell death was investigated by the use of drugs Thapsigargin (Tg) and Chloroquine (CQ) with prior induction and or blockade of autophagy and apoptosis which modulated the ER stress response and resultant form of cell death. All these biological processes can be measured flow cytometrically allowing the determination of the type of cell death, G1 cell cycle arrest, cell cycle dependent measurement of ER stress transducer PERK, misfolded proteins, reticulophagy, and autophagy marker LC3B. Jurkat cells after Tg or CQ treatment became necrotic and apoptotic, showed G1 cell cycle arrest, autophagy, and ER stress. Prior induction of autophagy before ER stress increased levels of necrotic and apoptotic cell death. Autophagy was further up-regulated, while PERK was reduced or abrogated. CQ showed reduced levels of misfolded proteins and reticulophagy, while Tg showed no change in misfolded protein levels but increased reticulophagy and thus displayed more ER stress. Prior blockade of apoptosis before induction of ER stress resulted in cell survival except with high Tg levels which induced necrosis. Autophagy was up-regulated with modulation of PERK and reticulophagy levels with an abrogation of the misfolded protein response. Blockade of apoptosis with induction of autophagy before ER stress showed death by necrosis with high dose drugs and cell survival with low doses of drugs. CQ induced reduced levels G1 cell cycle arrest while it was maintained with Tg. Autophagy was also maintained with reduced levels of ER stress. These data demonstrates a profound link between the processes of ER stress, autophagy, and the resultant form of cell death all of which can be modulated depending upon the sequence and concentration of drugs employed.
关键词： misfolded proteins,autophagy,PERK,ER stress,reticulophagy
更新于2025-09-09 09:28:46