- 标题
- 摘要
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- 实验方案
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Near-infrared upconversion–activated CRISPR-Cas9 system: A remote-controlled gene editing platform
摘要： As an RNA-guided nuclease, CRISPR-Cas9 offers facile and promising solutions to mediate genome modification with respect to versatility and high precision. However, spatiotemporal manipulation of CRISPR-Cas9 delivery remains a daunting challenge for robust effectuation of gene editing both in vitro and in vivo. Here, we designed a near-infrared (NIR) light–responsive nanocarrier of CRISPR-Cas9 for cancer therapeutics based on upconversion nanoparticles (UCNPs). The UCNPs served as “nanotransducers” that can convert NIR light (980 nm) into local ultraviolet light for the cleavage of photosensitive molecules, thereby resulting in on-demand release of CRISPR-Cas9. In addition, by preparing a single guide RNA targeting a tumor gene (polo-like kinase-1), our strategies have successfully inhibited the proliferation of tumor cell via NIR light–activated gene editing both in vitro and in vivo. Overall, this exogenously controlled method presents enormous potential for targeted gene editing in deep tissues and treatment of a myriad of diseases.
关键词： cancer therapeutics,upconversion nanoparticles,gene editing,CRISPR-Cas9,near-infrared
更新于2025-11-21 11:08:12
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Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles
摘要： Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. UCNP applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb,Er,Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin9-29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, non-cytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.
关键词： nanotoxicology,pharmacodynamics,pharmacokinetics,animal imaging,upconversion nanoparticles,photoluminescent nanomaterials
更新于2025-11-21 11:08:12
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Dopamine-functionalized upconversion nanoparticles as fluorescent sensors for organophosphorus pesticide analysis
摘要： Organophosphorus pesticide (OP) residues in agricultural products, herbal medicines and environment have attracted increasing concerns because they cause high healthy risk. Herein, a tyrosinase-mediated photoinduced electron transfer system was constructed for OPs analysis by using dopamine-functionalized upconversion nanoparticles (UCNPs) as fluorescent (FL) sensors. Dopamine quinone was produced by tyrosinase-mediated oxidation of dopamine on the surface of UCNPs, which acted as electron accepter to quench the FL emission of UCNPs. The FL quenching was inhibited by OP since it inhibited the activity of tyrosinase. Chlorpyrifos was used as a model analyte to investigate the feasibility of the FL sensor for the analysis of OPs. Under the optimal conditions, chlorpyrifos can be analysed in a wide range of 1.0 ? 1000 ng mL?1, with a detection limit of 0.38 ng mL?1 (3σ). Some other groups pesticides, including organonitrogen pesticide, organochlorine pesticide and chloronicotinyl insecticide all showed negligible interference. The proposed sensor was successfully used to analyse chlorpyrifos spiked in Balloonflower and Angelica with acceptable recovery values of 95.4–120.0%, demonstrating its application potential for real samples. It exhibits some advantages like low cost, high sensitivity and free of autofluorescent interference and photobleaching.
关键词： Tyrosinase,Photoinduced electron transfer,Fluorescent sensor,Organophosphorus pesticide,Upconversion nanoparticles,Chlorpyrifos
更新于2025-11-14 17:15:25
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Simultaneous enhancement of red upconversion luminescence and CT contrast of NaGdF <sub/>4</sub> :Yb,Er nanoparticles <i>via</i> Lu <sup>3+</sup> doping
摘要： To date, lanthanide-doped upconversion nanoparticles (UCNPs) have been widely reported as a promising CT contrast agent because they have high atomic numbers and big X-ray attenuation coefficient values. However, it is still a challenge to fabricate a simple multimodal imaging probe with improved image quality for early cancer diagnosis in clinical medicine. Herein, ultra-small, uniform and monodisperse β-NaGdF4:Yb,Er,X% Lu (X = 0, 1, 2.5, 4, 6, 7.5) UCNPs were prepared through a solvothermal method with high-level modulation of both the phase and morphology. Meanwhile, a remarkably enhanced red upconversion luminescence (UCL) in the β-NaGdF4:Yb,Er,X% Lu NPs was successfully realized via Lu3+ doping. It is found that as the content of Lu3+ increases from 0 to 7.5 mol%, the UCL intensity of the red emission first increases and then decreases, with the optimum doping content of Lu3+ ions of 2.5 mol%. The red UCL enhancement is ascribed to the change of the Yb–Er interionic distance controlling the Yb–Er energy transfer rate and the distortion of the local environment of Er3+ ions influencing the 4f–4f transition rates of Er3+ ions, which has been further confirmed by the experimental check of the crystallographic phase and by photoluminescence spectroscopy employing Eu3+ as the structural probe, respectively. More importantly, after being modified with the HS-PEG2000-NH2 ligand, the NH2-PEGylated-NaGdF4:Yb,Er,X% Lu NPs exhibited low cytotoxicity, high biocompatibility, and remarkably enhanced contrast performance in in vitro UCL and in vivo CT imaging. On the basis of our findings, the as-obtained functionalized UCNPs could be considered as a promising versatile dual-mode imaging probe for bioimaging, tumor diagnosis, and cancer therapy.
关键词： red luminescence enhancement,Lu3+ doping,upconversion nanoparticles,multimodal imaging,CT contrast
更新于2025-11-14 17:04:02
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Upconversion fluorescent nanoparticles based-sensor array for discrimination of the same variety red grape wines
摘要： In this research, a novel fluorescent sensor array based on upconversion nanomaterials (UCNPs) for the discrimination of the same variety red grape wines from different manufacturers was developed. The sensor array was composed of six elements: one positively charged UCNPs modified with guanidine groups (UCNPs@GDN), two negatively charged UCNPs modified with sulfonic acid groups (UCNPs@SO3H) and phosphonic acid groups (UCNPs@PO(OH)2), respectively, and their mixture 1 (UCNPs@GDN + UCNPs@SO3H), mixture 2 (UCNPs@GDN + UCNPs@PO(OH)2) and mixture 3 {UCNPs@GDN + UCNPs@SO3H + UCNPs@PO(OH)2}. The discrimination mechanism is mainly attributed to the emission of those upconversion fluorescent nanoparticles being quenched by organic ingredients that usually exist in red grape wines. The discrimination of red grape wines was carried out by employing UCNPs@GDN, UCNPs@SO3H and UCNPs@PO(OH)2 in pH = 7.0 HEPES buffer, the mixture 1 and mixture 2 in pH = 9.0 PBS buffer, and mixture 3 in pH = 6.0 Tris–HCl buffer. Principal component analysis (PCA) of the data obtained from our established array showed obvious distinction among the nine red grape wines from different manufacturers. The present work is expected to inspire more marvellous research in the fields of UCNPs and red grape wines identification.
关键词： red grape wines,fluorescence quenching,sensor array,upconversion nanoparticles,discrimination
更新于2025-11-14 15:18:02
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Enhanced upconversion luminescence intensity of core-shell NaYF4 nanocrystals guided by morphological control
摘要： How to further increase the upconversion luminescence (UCL) efficiency of core-shell upconversion nanoparticles (UCNPs) is highly desirable for their photoelectric and biological applications. Herein, a novel but facile strategy is proposed to substantially enhance the UCL intensity of NaYF4 based core-shell UCNPs by morphological control. The morphologies of core-shell UCNPs can be optimized from rod-like to spherical like by changing the ratio of oleic acid (OA) to 1-octadecene (ODE) during the shell growth process with other reaction conditions constant. The mechanism of shape control is further investigated based on the competitive absorption between OA molecules and lanthanide ions (Y3+, Yb3+, Er3+ or Tm3+) onto the different crystal axes (a, b and c) to guide their shell growth speed. The absolute quantum yields were up to 2.7 % and 1.8 % for spherical and rod like core-shell UCNPs under excitation of 980 nm laser (power density of 1.6 W/cm2), respectively. Moreover, the UCL intensity and effective lifetime (τeff) of Er3+ emission at 541 nm of spherical like core-shell UCNPs increased by 11.7 and 1.82 folds than rod like core-shell UCNPs. Therefore, our designed novel strategy can greatly improve the UCL efficiency of core-shell UCNPs and promote their development in diverse applications.
关键词： upconversion nanoparticles,upconversion luminescence,core-shell structure,morphological control
更新于2025-09-23 15:23:52
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Highly selective and sensitive detection of catecholamines using NaLuGdF4:Yb3+/Er3+ upconversion nanoparticles decorated with metal ions
摘要： We developed a novel optical sensor for sensitive and selective detection of catecholamines based on upconversion nanoparticles (UCNPs) decorated with different metal ions (UCNP-Men+). 1,2-ethanedithiol was chosen as a surface additive to synthesize the NaLuGdF4:Yb3+/Er3+ UCNPs by one-step at 200 °C. The as-prepared UCNPs exhibited a strong emission under the continuous excitation at 980 nm. It was found that catecholamines could be more effectively detected in the presence of UCNP-Fe3+, whereas, dopamine and epinephrine were detected selectively using UCNP-Li+ and UCNP-Cu2+ sensors, respectively. Under the optimum conditions, the limit of detections (LODs) for catecholamines, dopamine, and epinephrine are 2.8, 2.5, and 2.4 nM, respectively, with good linearity in the range of 5–320 nM for total catecholamines and 5–30 nM for dopamine and epinephrine. The developed method has been successfully applied to detect dopamine and epinephrine in human urine samples with good accuracy and satisfactory recovery.
关键词： Upconversion nanoparticles,Human urine,Metal ion decorated,Catecholamines,1,2-ethanedithiol
更新于2025-09-23 15:23:52
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Recent Trends Concerning Upconversion Nanoparticles and Near-IR Emissive Lanthanide Materials in the Context of Forensic Applications
摘要： Upconversion nanoparticles (UCNPs) are materials that, upon absorbing multiple photons of low energy (e.g. infrared radiation), subsequently emit a single photon of higher energy, typically within the visible spectrum. The physics of these materials have been the subject of detailed investigations driven by the potential application of these materials as medical imaging devices. One largely overlooked application of UCNPs is forensic science, wherein the ability to produce visible light from infrared light sources would result in a new generation of fingerprint powders that circumvent background interference which can be encountered with visible and ultraviolet light sources. Using lower energy, infrared radiation would simultaneously improve the safety of forensic practitioners who often employ light sources in less than ideal locations. This review article covers the development of UCNPs, the use of infrared radiation to visualise fingerprints by the forensic sciences, and the potential benefits of applying UCNP materials over current approaches.
关键词： Upconversion nanoparticles,Fingerprint visualisation,Near-IR emissive lanthanide materials,Forensic applications,NIR emission
更新于2025-09-23 15:22:29
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Near-Infrared Light Triggered Sulfur Dioxide Gas Therapy of Cancer
摘要： The exploitation of gas therapy platforms holds great promise as a 'green' approach for selective cancer therapy, however, it is often associated with some challenges, such as uncontrolled or insufficient gas generation and unclear therapeutic mechanisms. In this work, a gas therapy approach based on near-infrared (NIR) light triggered sulfur dioxide (SO2) generation was developed, and the therapeutic mechanism as well as in vivo anti-tumor therapeutic efficacy was demonstrated. A SO2 prodrug-loaded rattle-structured upconversion@silica nanoparticles (RUCSNs) was constructed to enable high loading capacity without obvious leakage, and to convert NIR light into ultraviolet (UV) light so as to activate the prodrug for SO2 generation. In addition, SO2 prodrug-loaded RUCSNs showed high cell uptake, good biocompatibility, intracellular tracking ability, and high NIR light triggered cytotoxicity. Furthermore, the cytotoxic SO2 was found to induce cell apoptosis accompanied with the increase of intracellular reactive oxygen species (ROS) levels and the damage of nuclear DNA. Moreover, efficient inhibition of tumor growth was achieved, associated with significantly prolonged survival of mice. Such NIR light-triggered SO2 therapy may provide an effective strategy to stimulate further development of synergistic cancer therapy platforms.
关键词： upconversion nanoparticles (UCNPs),gas therapy,cancer therapy,near-infrared (NIR),sulfur dioxide (SO2)
更新于2025-09-23 15:22:29
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Local Overheating of Biotissue Labeled With Upconversion Nanoparticles Under Yb3+ Resonance Excitation
摘要： Local overheating of biotissue is a critical step for biomedical applications, such as photothermal therapy, enhancement of vascular permeability, remote control of drug release, and so on. Overheating of biological tissue when exposed to light is usually realized by utilizing the materials with a high-absorption cross section (gold, silica, carbon nanoparticles, etc.). Here, we demonstrate core/shell NaYF4:Yb3+, Tm3+/NaYF4 upconversion nanoparticles (UCNPs) commonly used for bioimaging as promising near-infrared (NIR) absorbers for local overheating of biotissue. We assume that achievable temperature of tissue labeled with nanoparticles is high enough because of Yb3+ resonance absorption of NIR radiation, whereas the use of auxiliary light-absorbing materials or shells is optional for photothermal therapy. For this purpose, a computational model of tissue heating based on the energy balance equations was developed and verified with the experimentally obtained thermal-graphic maps of a mouse in response to the 975-nm laser irradiation. Labeling of biotissue with UCNPs was found to increase the local temperature up to 2?C compared to that of the non-labeled area under the laser intensity lower than 1 W/cm2. The cellular response to the UCNP-initiated hyperthermia at subcritical ablation temperatures (lower than 42?C) was demonstrated by measuring the heat shock protein overexpression. This indicates that the absorption cross section of Yb3+ in UCNPs is relatively large, and microscopic temperature of nanoparticles exceeds the integral tissue temperature. In summary, a new approach based on the use of UCNP without any additional NIR absorbers was used to demonstrate a simple approach in the development of photoluminescent probes for simultaneous bioimaging and local hyperthermia.
关键词： near-infrared irradiation,local overheating,photothermal material,bioimaging,heat shock proteins,biotissue laser heating,hyperthermia,upconversion nanoparticles
更新于2025-09-23 15:21:01