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Targeting fluorescent nanodiamonds to vascular endothelial growth factor receptors in tumor
摘要： The increased expression of vascular endothelial growth factor (VEGF) and its receptors is associated with angiogenesis in a growing tumor, presenting potential targets for tumor-selective imaging by way of targeted tracers. Though fluorescent tracers are used for targeted in vivo imaging, the lack of photostability and biocompatibility of many current fluorophores hinder their use in several applications involving long-term, continuous imaging. To address these problems, fluorescent nanodiamonds (FNDs), which exhibit infinite photostability and excellent biocompatibility, were explored as fluorophores in tracers for targeting VEGF receptors in growing tumors. To explore FND utility for imaging tumor VEGF receptors, we used click-chemistry to conjugate multiple copies of an engineered single-chain version of VEGF site-specifically derivatized with trans-cyclooctene (scVEGF-TCO) to 140 nm FND. The resulting targeting conjugates, FND-scVEGF, were then tested for functional activity of the scVEGF moieties through biochemical and tissue culture experiments and for selective tumor uptake in Balb/c mice with induced 4T1 carcinoma. We found that FND-scVEGF conjugates retain high affinity to VEGF receptors in cell culture experiments and observed preferential accumulation of FND-scVEGF in tumors relative to untargeted FND. Microspectroscopy provided unambiguous determination of FND within tissue by way of the unique spectral shape of nitrogen-vacancy induced fluorescence. These results validate and invite the use of targeted FND for diagnostic imaging and encourage further optimization of FND for fluorescence brightness.
关键词： Vascular Endothelial Growth Factor,Oncology,Targeted Fluorescence Imaging,Nanodiamond,Angiogenesis
更新于2025-11-21 11:24:58
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Graphene quantum dot based charge-reversal nanomaterial for nucleus-targeted drug delivery and efficiency controllable photodynamic therapy
摘要： Graphene quantum dots (GQD), the new zero-dimensional carbon nanomaterial, has been demonstrated as a promising material for biomedical applications due to its good biocompatibility and low toxicity. However, the integration of multiple therapeutic approaches into a nano-sized platform based on the GQD has not been explored yet to our best knowledge. In this report, we regulate the generation of reactive oxygen species (ROS) when using the GQD as a photosensitizer by varying the doping amount of nitrogen atoms to achieve efficiency controllable photodynamic therapy (PDT). On the other hand, charge-reversal (3-Aminopropyl) triethoxysilane (APTES) was employed to conjugate on the surface of GQD for nucleus targeting drug delivery for the first time. The treatment outcome of produced ROS and nucleus-targeting drug delivery was investigated by fluorescence imaging. The results demonstrated that the N-GQD-DOX-APTES in dual roles as a drug carrier and photosensitizer could achieve nucleus-targeting delivery and strong ROS production simultaneously. This approach provides a promising strategy for the development of multifunctional therapy in one nano platform for biomedical applications.
关键词： nucleus-targeted drug delivery,Graphene quantum dots,nitrogen doped graphene quantum dots,charge-reversal,photodynamic therapy
更新于2025-11-21 11:24:58
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Design and synthesis of a new fluorescent probe for cascade detection of Zn <sup>2+</sup> and H <sub/>2</sub> PO <sub/>4</sub><sup>?</sup> in water and targeted imaging of living cells
摘要： Design and synthesis of new fluorescence probes with good water‐solubility is of great importance to better understanding the significant role of ions which are related to biology and the environment. As important ions, zinc ion (Zn2+) and dihydrogen phosphate ion (H2PO4?) display essential roles in living systems, and quantitative detection of these ions in water is still a challenge. In order to consider the significant role of the galactose moiety in the design of a water‐soluble fluorescence sensor, herein, we have developed a novel probe, Gal‐AQTF, for the cascade detection of Zn2+ and H2PO4? with excellent selectivity in water. Through the introduction of the galactose moiety onto the sensor AQTF, which has been reported earlier by us, the water‐solubility, cell compatibility and targeting ability were enhanced. Gal‐AQTF has been successfully applied in the imaging of the living cells of HepG2 and A549, and illustrated good selectivity for the HepG2 cells which overly express the asialoglycoprotein (ASGP) receptor.
关键词： targeted imaging,Galactose,Zn2+ and H2PO4?,in water,fluorescent probe
更新于2025-11-21 11:24:58
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Visualizing Nitric Oxide in Mitochondria and Lysosomes of Living Cells with N-Nitrosation of BODIPY-based Fluorescent Probes
摘要： Nitric oxide (NO), a ubiquitous gasotransmitter which plays critical roles in cardiovascular, nervous, and immune systems related diseases, is closely related in the physiological and pathological processes of mitochondria and lysosomes. Thus, monitoring NO in mitochondria or lysosomes is very meaningful for NO related chemical biology. Herein, we rationally designed four NO probes, BDP-NO, Mito-NO-T, Mito-NO and Lyso-NO, based on BODIPY dye substituted at meso position with 5-amino-2-methoxy-phenyl scaffold. These four probes all showed fast fluorescence off-on response toward NO with excellent selectivity and high sensitivity with the detection limit of BDP-NO to reach 5.7 nM. We introduced triphenylphosphonium and morpholine moieties onto BODIPY scaffold respectively to enable organelle-targetability. MTT and flow cytometry assay demonstrated that the probes exhibited low cytotoxicity, which was beneficial to the biological application in living cells. Confocal fluorescence microscopy experiments confirmed excellent mitochondria targeting for Mito-NO and lysosome-targeting with Lyso-NO for the detection of NO in living cells.
关键词： Fluorescent probes,Mitochondria-targeted,Lysosomes-targeted,BODIPY,Nitric oxide
更新于2025-11-21 11:08:12
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Lysosome-Targeted Single Fluorescence Probe for Two-Channel Imaging Intracellular SO2 and Biothiols
摘要： As the members of reactive sulfur species, SO2 and biothiols play a signi?cant role in physiological and pathological processes and directly in?uence numerous diseases. Furthermore, SO2 and biothiols can provide a reductive environment for lysosomes to carry out their optimal functionality. To this end, the development of single ?uorescent probes for imaging SO2 and biothiols from different emission channels is highly desirable for understanding their physiological nature. Here, a lysosome-targeted ?uorescent probe (BPO-DNSP) with a dual reaction site for SO2 and biothiols was presented. BPO-DNSP can sensitively and selectively respond to SO2 in the green channel with a large Stokes shift over 105 nm, and to biothiols in the near-infrared emission channel with a large Stokes shift over 109 nm. The emission shift for the two channels was as high as 170 nm. Colocalization experiments veri?ed that BPO-DNSP can selectively enrich lysosomes. Notably, BPO-DNSP can not only be used to image intracellular SO2 and biothiols from two different channels, but also to monitor the conversion of biothiols to SO2 without adding exogenous enzymes in living HeLa cells.
关键词： ?uorescence imaging,lysosome-targeted,single ?uorescent probe,biothiols,SO2
更新于2025-11-21 11:08:12
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Microwave-Assisted Synthesis of Quasi-Pyramidal CuInS <sub/>2</sub> -ZnS Nanocrystals for Enhanced Near-Infrared Targeted Fluorescent Imaging of Subcutaneous Melanoma
摘要： Near-infrared (NIR) fluorescent CuInS2–ZnS nanocrystals (CIZS NCs) are synthesized via an ultra-fast, non-injection microwave (MW)-assisted nanoalloying process at 230 oC within 5 min using 1-dodecanethiol (DDT) as both the sulfur source and solvent under solvothermal (ST) condition. The structural and surface analyses reveal that DDT-functionalized CIZS NCs exhibit quasi-pyramids of tetragonal-phase with well-defined facets. The DDT-functionalized CIZS NCs present a photoluminescence quantum yield (PLQY) of 76% and a long-lived fluorescence lifetime of ≈0.6 μs in organic-phase. Subsequently, DDT-functionalized CIZS NCs are phase-transferred via ligand-exchange using 11-mercaptoundecanoic acid (MUA) into water-soluble MUA–CIZS NCs that exhibit a substantial PLQY of 55%. In addition, the NIR-fluorescent MUA-functionalized CIZS NCs in conjugation with folic acid (FA), as a tumor-targeting ligand, demonstrates enhanced tumor-targeted imaging ability. The FA–MUA–CIZS NC conjugates exhibit a cell viability of ≈75% even at the highest concentration of 1 mg mL–1 and a labeling efficiency of 95.4%. The in vivo imaging results corroborate that FA–MUA–CIZS NCs conjugates are actively targeted to folate receptor-positive B16F10 tumor-bearing C57BL/6 mice in 2 h. The histopathological and hematological studies confirm no significant changes in tissue architecture and blood biochemical parameters. The confocal microscopy studies reveal deep penetration and uniform distribution of FA–MUA–CIZS NCs conjugates in subcutaneous melanoma.
关键词： CuInS2–ZnS nanocrystals,nano-bioprobe,nanoalloying approach,targeted bioimaging,microwave-solvothermal method
更新于2025-11-21 11:08:12
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A mitochondria-targeted ratiometric fluorescent probe for detection of SO2 derivatives in living cells and in vivo
摘要： A new near-infrared (NIR) ?uorescent probe for colorimetric and ratiometric detection of SO2 derivatives was developed based on conjugated hybrid coumarin-hemicyanine. The probe can detect HSO3?/SO32? in HEPES bu?er (10 mM, pH 7.4, with 10% DMF, v/v) with a large emission shift (259 nm). Importantly, it was successfully used for ?uorescence imaging of endogenous bisul?te in BT-474 cells and zebra?sh.
关键词： Near-infrared ?uorescent probe,SO2 derivatives,Mitochondria-targeted,Ratiometric,Colorimetric
更新于2025-11-19 16:56:35
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In Situ Synthesis of Fluorescent Mesoporous Silica–Carbon Dot Nanohybrids Featuring Folate Receptor-Overexpressing Cancer Cell Targeting and Drug Delivery
摘要： Multifunctional nanocarrier-based theranostics is supposed to overcome some key problems in cancer treatment. In this work, a novel method for the preparation of a fluorescent mesoporous silica–carbon dot nanohybrid was developed. Carbon dots (CDs), from folic acid as the raw material, were prepared in situ and anchored on the surface of amino-modified mesoporous silica nanoparticles (MSNs–NH2) via a microwave-assisted solvothermal reaction. The as-prepared nanohybrid (designated MSNs–CDs) not only exhibited strong and stable yellow emission but also preserved the unique features of MSNs (e.g., mesoporous structure, large specific surface area, and good biocompatibility), demonstrating a potential capability for fluorescence imaging-guided drug delivery. More interestingly, the MSNs–CDs nanohybrid was able to selectively target folate receptor-overexpressing cancer cells (e.g., HeLa), indicating that folic acid still retained its function even after undergoing the solvothermal reaction. Benefited by these excellent properties, the fluorescent MSNs–CDs nanohybrid can be employed as a fluorescence-guided nanocarrier for the targeted delivery of anticancer drugs (e.g., doxorubicin), thereby enhancing chemotherapeutic efficacy and reducing side effects. Our studies may provide a facile strategy for the fabrication of multifunctional MSN-based theranostic platforms, which is beneficial in the diagnosis and therapy of cancers in future.
关键词： Targeted drug delivery,Fluorescence imaging,Mesoporous silica nanoparticles,Carbon dots,Chemotherapy
更新于2025-11-14 14:48:53
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Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy
摘要： Ultrasound molecular imaging as a promising strategy, which involved the use of molecularly targeted contrast agents, combined the advantages of contrast-enhanced ultrasound with the photothermal effect of reduced graphene oxide (rGO). Methods and results: The heparin sulfate proteoglycan glypican-3 (GPC3) is a potential molecular target for hepatocellular carcinoma (HCC). In this study, we covalently linked biotinylated GPC3 antibody to PEGylated nano-rGO to obtain GPC3-modified rGO-PEG (rGO-GPC3), and then combined rGO-GPC3 with avidinylated nanobubbles (NBs) using biotin-avidin system to prepare NBs-GPC3-rGO with photothermal effect and dispersibility, solubility in physiological environment. The average size of NBs-GPC3-rGO complex was 700.4±52.9 nm due to the polymerization of biotin-avidin system. Scanning electron microscope (SEM) showed NBs-GPC3-rGO attached to human hepatocellular carcinoma HepG2 cell. The ultrasound-targeted nanobubble destruction (UTND) technology make use of the physical energy of ultrasound exposure for the improvement of rGO delivery. Compared with other control groups, the highest nanobubble destruction efficiency of NBs-GPC3-rGO was attributed to the dissection effect of rGO on UTND. This is a positive feedback effect that leads to an increase in the concentration of rGO around the HepG2 cell. So NBs-GPC3-rGO using UTND and near-infrared (NIR) irradiation resulted in cell viability within 24 h, 48 h, 72 h lower than other treatment groups. Conclusion: This work established NBs-GPC3-rGO as an ultrasonic photothermal agent due to its suitable size, imaging capability, photothermal efficiency for visual photothermal therapy in vitro.
关键词： ultrasound-targeted nanobubble destruction,photothermal therapy,glypican-3,reduced graphene oxide,HepG2 cell
更新于2025-09-23 15:23:52
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Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant
摘要： Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD. Here, we examine oxidative processes induced in rabbit retina by excessive light illumination with or without premedication using mitochondria-targeted antioxidant SkQ1 (10-(6’-plastoquinonyl)decyltriphenyl-phosphonium). The retinal extracts obtained from animals euthanized within 1–7 days post exposure were analyzed for H2O2, malondialdehyde (MDA), total antioxidant activity (AOA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) using colorimetric and luminescence assays. Oxidation of visual arrestin was monitored by immunoblotting. The light exposure induced lipid peroxidation and H2O2 accumulation in the retinal cells. Unexpectedly, it prominently upregulated AOA in retinal extracts although SOD and GPx activities were compromised. These alterations were accompanied by accumulation of disulfide dimers of arrestin revealing oxidative stress in the photoreceptors. Premedication of the eyes with SkQ1 accelerated normalization of H2O2 levels and redox-status of lipids and proteins, contemporarily enhancing AOA and, likely, sustaining normal activity of GPx. Thus, SkQ1 protects the retina from light-induced oxidative stress and could be employed to suppress oxidative damage of proteins and lipids contributing to AMD.
关键词： SkQ1,superoxide dismutase,glutathione peroxidase,disulfide dimerization of proteins,visual arrestin,age-related macular degeneration,mitochondria-targeted antioxidant,antioxidant activity,light-induced retinal damage,oxidative stress
更新于2025-09-23 15:23:52