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Melanin-like nanoparticles decorated with an autophagy-inducing peptide for efficient targeted photothermal therapy
摘要： Photothermal therapy efficiently ablates tumors via hyperthermia but inevitably induces serious side effects including thermal damage to normal tissues, inflammations and enhanced risk of tumor metastasis. In this study, we fabricated a dual peptide decorated melanin-like nanoparticle for tumor-targeted and autophagy-promoted photothermal therapy in pursuit of improved cancer treatment. The multifunctional nanoparticle was composed of dual peptide RGD- and beclin 1-modified and PEGylated melanin-like polydopamine nanoparticles. Beclin 1-derived peptide modified on the nanoparticle up-regulated autophagy in cancer cells and further sensitized the photothermal ablation to tumors. RGD decorated on the particle surface enhanced the selectivity and cellular uptake of polydopamine nanoparticles by breast cancer cells. In vivo therapeutic experiments revealed that the tumor-targeted and autophagy promotion-associated photothermal therapy efficiently regressed tumors at a low temperature around 43 oC. The study provides a novel and efficient strategy to improve the efficiency of photothermal therapy via the up-regulation of autophagy in tumor cells.
关键词： photothermal therapy,beclin 1,multifunctional nanoparticles,autophagy,melanin-like
更新于2025-11-19 16:56:35
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A Photostable AIEgen for Specific and Real-time Monitoring of Lysosomal Processes
摘要： Lysosomes are recognized as advanced organelles involved in many cellular processes, and are also considered as crucial regulators of cell homeostasis. The current strategies for monitoring activities of lysosomes exhibit some limitations. Herein, we synthesized a novel fluorescent probe named 2M-DPAS with AIE characteristics, which was proved to have significant advantages of good biocompatibility, high selectivity, bright emission and excellent photostability. Based on those, 2M-DPAS can be used to continuously monitor the dynamic changes of lysosomes including autophagy and mitophagy, as well as to track the process of endocytosis of macromolecules in lysosomes, which are benefit to better know about the lysosomes-related diseases.
关键词： Aggregation-induced emission,Lysosomes,Autophagy,Monitoring,Phagocytosis of macromolecules
更新于2025-09-23 15:23:52
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Retinal photoreceptor apoptosis is associated with impaired serum ionized calcium homeostasis in diabetic retinopathy: An in-vivo analysis
摘要： Purpose: The aim of this work was to study the association of serum ionized calcium with retinal photoreceptor apoptosis on spectral domain optical coherence tomography (SD-OCT) in diabetic retinopathy (DR). Methods: Sixty consecutive cases with Type 2 diabetes mellitus were categorized into three groups: no diabetic retinopathy; non-proliferative DR; proliferative DR. The eye with more severe form of the disease was considered. Twenty healthy controls were also included. Best corrected visual acuity (BCVA) was measured on logMAR scale. Retinal photoreceptor apoptosis was defined as disruption of retinal photoreceptor ellipsoid zone (EZ). Ellipsoid zone disruption was assessed using SD-OCT. Serum levels of total and ionized calcium were measured using standard protocol. Results: EZ disruption was found to be positively associated with serum total calcium and ionized calcium. Also, EZ disruption was found to be positively associated with logMAR BCVA. Conclusion: Increased serum ionized calcium induces retinal photoreceptor apoptosis resulting in increased EZ disruption in DR.
关键词： Ionized calcium,Retinal photoreceptor apoptosis,Diabetic retinopathy,Autophagy,Ellipsoid zone,Spectral-domain optical coherence tomography
更新于2025-09-23 15:23:52
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Hyperbaric oxygen combined with 5-aminolevulinic acid photodynamic therapy inhibited human squamous cell proliferation
摘要： The photodynamic therapy (PDT) depends on the presence of molecular oxygen. Thus, the efficiency of PDT is limited in anoxic regions of tumor tissue and vascular shutdown. It is reported the use of hyperbaric oxygen (HBO) may enhance the efficiency of PDT. However, there are rarely studies about utilizing HBO plus PDT for treatment with human squamous cell carcinoma (SCC). Therefore, this study aimed to investigate and compare the therapeutic effect of combined therapy and PDT alone treatment. Multiple cellular and molecular biology techniques were used in the current study such as CCK-8, western blotting, flow cytometry, MDC staining and immunofluorescence assay. The results of combination index indicated that HBO combination with PDT synergistically inhibited A431 cells proliferation in vitro. In addition, we found that HBO significantly enhanced PDT-induced cell apoptosis via increasing the active caspase-3, active caspase-9, Apaf-1 and Bax levels and down-regulating Bcl-2. Meanwhile, the result of MDC and immunofluorescence assay confirmed that HBO increased PDT-induced autophagosome formation in A431 cells. Interestingly, autophagy inhibitor 3-methyladenine (3-MA) further increased combination-induced cell apoptosis by increasing the levels of active-caspase 9 and Apaf-1. Our results showed that HBO combined with PDT markedly induced A431 cells apoptosis and autophagy. Nevertheless, autophagy play a pro-survival role against apoptosis. Thus, HBO combination with PDT may constitute a promising approach to treat human squamous cell carcinoma in the future.
关键词： human squamous cell carcinoma,5-aminolevulinic acid photodynamic therapy,apoptosis,autophagy,hyperbaric oxygen
更新于2025-09-23 15:23:52
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Cell death mechanisms in a mouse model of retinal degeneration in Spinocerebellar ataxia 7
摘要： Spino-cerebellar ataxia type 7 (SCA7) is a polyglutamine (polyQ) disorder characterized by neurodegeneration of the brain, cerebellum, and retina caused by a polyglutamine expansion in ataxin 7. The presence of an expanded polyQ tract in a mutant protein is known to induce protein aggregation, cellular stress, toxicity, and finally cell death. However, the consequences of the presence of mutant ataxin7 in the retina and the mechanisms underlying photoreceptor degeneration remain poorly understood. In this study, we show that in a retinal SCA7 mouse model, polyQ ataxin7 induces stress within the retina and activates Muller cells. Moreover, Unfolded Protein Response and autophagy are activated in SCA7 photoreceptors. We have also shown that the photoreceptor death does not involve a caspase-dependent apoptosis but instead involves apoptosis inducing factor (AIF) and Leukocyte Elastase Inhibitor (LEI/L-DNase II). When these two cell death effectors are downregulated by their siRNA, a significant reduction of photoreceptor death is observed. These results highlight the consequences of polyQ protein expression in the retina and the role of caspase-independent pathways involved in photoreceptor cell death.
关键词： retina,toxicity,Spinocerebellar ataxia type 7,caspase-independent cell death,photoreceptors,polyglutamine disorder,autophagy,unfolded protein response
更新于2025-09-23 15:22:29
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[Methods in Molecular Biology] Autophagy Volume 1880 (Methods and Protocols) || Triggering Mitophagy with Photosensitizers
摘要： One can utilize light illumination to stimulate mitochondrial reactive oxygen species production through the use of mitochondria-specific photosensitizers. By proper tuning of the light dosage, the methodology permits probing of a multitude of mitochondrial damage responses, including mitophagy. This light-controllable trick offers unique opportunities for the investigation of mitophagy—one can spatiotemporally define mitochondrial damage, alter the number of impaired mitochondria, as well as modulate the severity of the mitochondrial injury. This light-activated mitophagy can be adapted not only to single-cell imaging techniques but also to cell population-based biochemical assays.
关键词： Mitophagy,Photosensitizer,Autophagy,MitoTracker Deep Red
更新于2025-09-23 15:22:29
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Regulation of autophagy orchestrates pyroptotic cell death in molybdenum disulfifide quantum dots-induced microglial toxicity
摘要： Molybdenum disulfifide quantum dots (MoS2 QDs) represents an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenides (TMDs) nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS2 QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS2 QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS2 QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS2 QDs-induced pyroptosis. Additionally, MoS2 QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavenger could diminish the MoS2 QDs-mediated NLRP3 inflammasomes activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS2 QDs exposure in microglial cells, affording novel insights into the neurotoxicity of MoS2 QDs, and facilitating the rational design and application of functional MoS2 QDs in neuroscience.
关键词： microglia,autophagy,neurotoxicity,MoS2 quantum dots,pyroptosis
更新于2025-09-23 15:19:57
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Essential contribution of macrophage Tie2 signal mediated autophagy in laser-induced choroidal neovascularization
摘要： Autophagy plays critical roles in various ocular diseases, including age-related macular degeneration (AMD). Tie2-expressing macrophages (TEMs) play crucial roles in angiogenesis. To investigate the role of TEMs and autophagy in the development of AMD, we employed macrophage-specific Tie2 knockout mice and used a laser-induced choroidal neovascularization (CNV). The results showed that TEMs can promote CNV formation by up-regulating the level of autophagy. These results were further verified by in vitro cell experiments that peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGF by activating AMPK signaling pathway. Our results suggest that TEMs and macrophage Tie2 signal mediated-autophagy play critical role in experimental CNV, and they may be novel preventive targets for AMD treatment.
关键词： Tie2-expressing macrophage (TEMs),Age-related macular degeneration,Choroidal neovascularization,Autophagy
更新于2025-09-23 15:19:57
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Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells
摘要： To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect. Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells. Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.
关键词： autophagy,apoptosis,photodynamic therapy,chloroquine,sinoporphyrin sodium,colorectal cancer
更新于2025-09-19 17:15:36
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Near-infrared light remotely up-regulate autophagy with spatiotemporal precision via upconversion optogenetic nanosystem
摘要： In vivo noninvasively manipulating biological functions by the mediation of biosafe near infrared (NIR) light is becoming increasingly popular. For these applications, upconversion rare-earth nanomaterial holds great promise as a novel photonic element, and has been widely adopted in optogenetics. In this article, an upconversion optogenetic nanosystem that was promised to achieve autophagy up-regulation with spatiotemporal precision was designed. The biocompatible system worked via two separated parts: blue light-receptor optogenetics-autophagy upregulation plasmids for import; and upconversion rods-encapsulated flexible capsule for converting tissue-penetrative NIR light into local visible blue light. Results validated that this system could achieve up-regulation of autophagy in vitro (in both HeLa and 293T cell lines) and remotely penetrate tissue (~3.5mm) in vivo. Since autophagy serves at a central position in intracellular signalling pathways, which is correlative with diverse pathologies, we expect that this method could establish an upconversion material-based autophagy up-regulation strategy for fundamental and clinical applications.
关键词： optogenetics,autophagy,upconversion materials,protein-protein interaction (PPI),near-infrared (NIR) light
更新于2025-09-19 17:15:36