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Gold-tagged Polymeric Nanoparticles with Spatially Controlled Composition for Enhanced Detectability in Biological Environments
摘要： Organic nanoparticles offer the advantage of high biocompatibility for biomedical applications but suffer frequently from poor visibility in biological environments. While fluorescent-labeling is convenient and allows for fast and extensive histological analysis, fluorescence imaging and quantitative analysis are limited by low resolution and significantly hindered by tissue auto-fluorescence. Labeling of polymeric nanoparticles with an additional gold tag would allow for high resolution imaging via transmission electron microscopy (TEM) and for quantification of particles by inductively coupled plasma optical emission spectrometry (ICP-OES). However, spatially uncontrolled gold-tagging can cause significant fluorescence quenching. To overcome this restraint, 2.2 nm gold nanoparticles were introduced at the interface between the hydrophobic fluorophore-loaded core and the hydrophilic shell of polymeric nanoparticles. Due to the small size of gold labels and the spatially controlled stratified composition of hybrid nanoparticles, fluorescence quenching by gold tags was minimized to 15.1%, allowing for concomitant detection of both labels via optical microscopy after enhancement of the gold tags. Multilayered hybrid nanoparticles exhibited outstanding detectability by transmission electron microscopy, even without additional sample staining. Furthermore, they were capable of producing remarkable image contrast inside cells after gold or silver enhancement. The interfacial gold layer increased the hydrodynamic particle size only marginally from 71.8 to 89.5 nm and had no negative impact on biocompatibility in vitro. The gold content (0.75% m/m) is sufficiently high for future quantification in tissues after systemic administration. With their clean-cut structure and superior detectability, multilayered hybrid nanoparticles constitute an outstanding blueprint and a precious tool for the development of nanomedicines.
关键词： gold,polymeric nanoparticles,hybrid,TEM,PLGA,contrast agent
更新于2025-11-21 11:24:58
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Novel Biodegradable Polymer Tethered Platinum (II) for Photoacoustic Imaging
摘要： Photoacoustic microscopy (PAM) is an emerging imaging diagnostic technique for various diseases. Coupled with contrast agents, photoacoustic (PA) imaging yields additional information to facilitate an accurate diagnosis. While many organic-based contrast agents, notably those of cyanine dyes, nanoparticles, polyhydroxy-fullerene and carbon nanotubes, have become available, the use of transition metal as contrast agent is scant. Here, for the first time, we report a platinum II-based biodegradable polymer for PA imaging that is capable of effective cellular internalization with very low cytotoxicity. The experiment results show great promise as a novel photoacoustic contrast agent as its detectable PA signal was observed both in cell imaging and in vivo rat cerebral vascular imaging via designed PAM. This work exemplifies the incorporation of transition metal complex with polymeric nanoparticles, further expanding the field of the ability of PA imaging.
关键词： Platinum,Biodegradable polymer,Photoacoustic imaging,Contrast agent,Transition metal
更新于2025-09-23 15:21:21
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Shell-free Copper Indium Sulfide Quantum Dots Induce Toxicity <i>In Vitro</i> and <i>In Vivo</i>
摘要： Semiconductor quantum dots (QDs) are attractive fluorescent contrast agents for in vivo imaging due to their superior photophysical properties, but traditional QDs comprise toxic materials such as cadmium or lead. Copper indium sulfide (CuInS2, CIS) QDs have been posited as a non-toxic and potentially clinically translatable alternative; however, previous in vivo studies utilized particles with a passivating zinc sulfide (ZnS) shell, limiting direct evidence of the biocompatibility of the underlying CIS. For the first time, we assess the biodistribution and toxicity of unshelled CIS and partially zinc-alloyed CISZ QDs in a murine model. We show that bare CIS QDs breakdown quickly, inducing significant toxicity as seen in organ weight, blood chemistry, and histology. CISZ demonstrate significant, but lower, toxicity compared to bare CIS, while our measurements of core/shell CIS/ZnS are consistent with literature reports of general biocompatibility. In vitro cytotoxicity is dose-dependent on the amount of metal released due to particle degradation, linking degradation to toxicity. These results challenge the assumption that removing heavy metals necessarily reduces toxicity: indeed, we find comparable in vitro cytotoxicity between CIS and CdSe QDs, while CIS caused severe toxicity in vivo compared to CdSe. In addition to highlighting the complexity of nanotoxicity and the differences between the in vitro and in vivo outcomes, these unexpected results serve as a reminder of the importance of assessing the biocompatibility of core QDs absent the protective ZnS shell when making specific claims of compositional biocompatibility.
关键词： in vivo imaging,biodegradable,CIS,nanotoxicity,nanomedicine,CuInS2,fluorescent contrast agent,QDs
更新于2025-09-19 17:13:59
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Fluorescein- and EGFR-Antibody Conjugated Silica Nanoparticles for Enhancement of Real-time Tumor Border Definition Using Confocal Laser Endomicroscopy in Squamous Cell Carcinoma of the Head and Neck
摘要： Intraoperative de?nition of tumor free resection margins in head and neck cancer is challenging. In the current proof-of-principle study we evaluated a novel silica nanoparticle-based agent for its potential use as contrast enhancer. We synthesized silica nanoparticles with an average size of 45 nm and modi?ed these particles with the ?uorescence stain ?uorescein isocyanate (FITC) for particle detection and with epidermal growth factor receptor (EGFR)-targeting antibodies for enhanced tumor speci?city. The nanoparticles exhibited good biocompatibility and could be detected in vitro and in vivo by confocal laser scanning microscopy. Additionally, we show in an ex vivo setting that these modi?ed nanoparticles speci?cally bind to tumor samples and could be detected using a handheld confocal ?uorescence endomicroscope. From a clinical point of view, we believe that this method could be used for tumor border contrast enhancement and for better intraoperative de?nition of R-0 tumor resection.
关键词： silica nanoparticles,EGFR,contrast agent
更新于2025-09-19 17:13:59
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[IEEE 2018 IEEE 8th International Conference Nanomaterials: Application & Properties (NAP) - Zatoka, Ukraine (2018.9.9-2018.9.14)] 2018 IEEE 8th International Conference Nanomaterials: Application & Properties (NAP) - Efficient Two-Photon Luminescence for Bioimaging Using Polymer Conjugations of Graphene Quantum Dots Based Materials
摘要： In this study, examination results revealed that conjugated polymers containing nitrogen and sulfur atoms lead to a higher quantum confinement of emissive energy trapped on the surface of material (graphene quantum dot (GQD)-polymers), resulting in a high luminescence quantum yield and impressive two-photon properties. Additionally, the GQD-polymers generated nonreactive oxygen species-dependent oxidative stress on cells. Furthermore, we demonstrated the effective use of two-photon excitation-mediated high two-photon luminescence intensity in an acidic environment enabled GQD-polymers to act as a promising contrast probe. When cancer cells are labeled with specific antibody GQD-polymers conjugates, molecular-specific imaging can be performed deep into a tissue phantom with extremely high signal-to-noise ratios. In situations in which imaging depths are limited by the maximum available power that can be delivered to the three-dimensional (3D) bioimaging plane without causing damage to tissue, GQD-polymers might provide sufficient brightness to extend the maximum depth of imaging. Moreover, we demonstrated that the use of GQD-polymers can expand the capabilities of two-photon imaging to allow noninvasive 3D bioimaging of a variety of new molecular signatures.
关键词： photostability,reactive oxygen species,three-dimensional bioimaging,photodynamic therapy,two-photon excitation,contrast probe,graphene,quantum dot-polymer,two-photon luminescence,two-photon,contrast agent,nitrogen-doped graphene quantum dots
更新于2025-09-16 10:30:52
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Endoplasmic reticulum stress involved in renal autophagy and dysfunction triggered by CdTe-quantum dots
摘要： Magnetic resonance imaging (MRI) is an indispensable imaging tool in clinical diagnosis of a wide range of diseases, including cancer.[1] The resolution of MRI could be further enhanced by using the MR contrast agent. However, the most widely used MR contrast agents, gadolinium based contrast agents, show potential toxicity to human, which can induce serious side effects such as nephrogenic systemic ?brosis (NSF). Therefore, a biocompatible MR contrast agent with considerable contrasting effect is urgently needed to ensure the safety and clinical performance of this technique.[2] In this study, novel manganese based nanobubbles were fabricated to function as a T1 contrast agent for MRI. The nanobubbles were demonstrated to have good contrasting effect as well as very low toxicity. The major metabolic clearance of these nanobubbles in vivo was demonstrated in mouse model. We also demonstrated that our nanobubbles are perfect drug carrier for MR imaging-guided chemotherapy. Our results suggest that biocompatible manganese based nanobubbles are a promising MR contrast agent for clinical diagnosis and treatment of tumors.[3]
关键词： MRI,Contrast agent,Toxicity,Cancer therapy
更新于2025-09-11 14:15:04
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Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging.
摘要： In this paper we show that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labelling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells (hMSCs). Cellular uptake was confirmed with bright field optical and transmission electron microscopy. The Gd(III)-SMNP labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found the photoacoustic signal increased as cell number increased (R2 = 0.96) indicating that such an approach could be employed to discriminate between stem cells populations with a limit of detection of 2.3 x 104 cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.
关键词： Photoacoustic Signal,Stem Cell Imaging,Gadolinium,Dual Modality Contrast Agent,Synthetic Melanin Nanoparticles
更新于2025-09-04 15:30:14