- 标题
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- 实验方案
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A highly sensitive living probe derived from nanoparticle-remodeled neutrophils for precision tumor imaging diagnosis
摘要： Timely and precise diagnosis of malignant tumors is of great value to patients’ treatment and prognosis. Although nanotechnology-based molecular imaging represents a major advancement in the field of tumor imaging diagnosis, it is restricted by the rapid blood clearance of nanoparticles and the diverse physiological barriers in vivo; hence, its further application is greatly hindered. Cell carriers, ascribed to their natural biological properties, are thus gaining increasing attention for addressing such issues. Here, taking full advantage of the inflammation-homing capability of neutrophils, we constructed a highly sensitive cell probe in which reduced bovine-serum albumin (BSA) nanoparticles, loaded with imaging agents (gadolinium (Gd) and BODIPY), were covalently fixed onto the cellular surface by 5-thio-2-nitrobenzoate (TNB)-mediated fast and efficient disulfide–thiol exchange. Impressively, the remodeling process exerted a negligible effect on the neutrophils’ biological profiles with regard to cell viability, morphology, and cell-surface protein markers. Compared with nanoparticle-based imaging agents in a lung-cancer xenograft model, the living neutrophil probe demonstrated faster targeting and stronger accumulation in the tumor site, as revealed by fluorescence and magnetic-resonance (MR) imaging. These results indicate the great potential of neutrophil-based living probe for precision tumor-diagnosis applications.
关键词： Biomaterials,Neutrophils,Nanoparticles,Molecular imaging,Tumor imaging
更新于2025-09-16 10:30:52
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BRET based dual-colour (visible/near-infrared) molecular imaging using a quantum dot/EGFP–luciferase conjugate
摘要： Owing to its high sensitivity, bioluminescence imaging is an important tool for biosensing and bioimaging in life sciences. Compared to fluorescence imaging, bioluminescence imaging has a superior advantage that the background signals resulting from autofluorescence are almost zero. In addition, bioluminescence imaging can permit long-term observation of living cells because external excitation is not needed, leading to no photobleaching and photocytotoxicity. Although bioluminescence imaging has such superior properties over fluorescence imaging, observation wavelengths in bioluminescence imaging are mostly limited to the visible region. Here we present bioluminescence resonance energy transfer (BRET) based dual-colour (visible/near-infrared) molecular imaging using a quantum dot (QD) and luciferase protein conjugate. This bioluminescent probe is designed to emit green and near-infrared luminescence from enhanced green fluorescent protein (EGFP) and CdSeTe/CdS (core/shell) QDs, where EGFP–Renilla luciferase (RLuc) fused proteins are conjugated to the QDs. Since the EGFP–RLuc fused protein contains an immunoglobulin binding domain (GB1) of protein G, it is possible to prepare a variety of molecular imaging probes functionalized with antibodies (IgG). We show that the BRET-based QD probe can be used for highly sensitive dual-colour (visible/near-infrared) bioluminescence molecular imaging of membrane receptors in cancer cells.
关键词： EGFP,luciferase,bioluminescence imaging,cancer cells,BRET,quantum dot,molecular imaging
更新于2025-09-16 10:30:52
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Deep-Tissue Photothermal Therapy Using Laser Illumination at NIR-IIa Window
摘要： Photothermal therapy (PTT) using near-infrared (NIR) light for tumor treatment has triggered extensive attentions because of its advantages of noninvasion and convenience. The current research on PTT usually uses lasers in the first NIR window (NIR-I; 700–900 nm) as irradiation source. However, the second NIR window (NIR-II; 1000–1700 nm) especially NIR-IIa window (1300–1400 nm) is considered much more promising in diagnosis and treatment as its superiority in penetration depth and maximum permissible exposure over NIR-I window. Hereby, we propose the use of laser excitation at 1275 nm, which is approved by Food and Drug Administration for physical therapy, as an attractive technique for PTT to balance of tissue absorption and scattering with water absorption. Specifically, CuS-PEG nanoparticles with similar absorption values at 1275 and 808 nm, a conventional NIR-I window for PTT, were synthesized as PTT agents and a comparison platform, to explore the potential of 1275 and 808 nm lasers for PTT, especially in deep-tissue settings. The results showed that 1275 nm laser was practicable in PTT. It exhibited much more desirable outcomes in cell ablation in vitro and deep-tissue antitumor capabilities in vivo compared to that of 808 nm laser. NIR-IIa laser illumination is superior to NIR-I laser for deep-tissue PTT, and shows high potential to improve the PTT outcome.
关键词： Molecular imaging,1275 nm laser,Deep-tissue,NIR-IIa,Photothermal therapy
更新于2025-09-16 10:30:52
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Quantum Dot-Based Simultaneous Multicolor Imaging
摘要： Quantum dots have attracted a great deal of attention among researchers in optical imaging because of their unique physicochemical properties. Their adjustable size allows quantum dots to emit visible fluorescence with different wavelengths excited by a single light source, allowing them to play an unmatched role in multitarget simultaneous multicolor imaging of tissues and cells compared with other molecular biotechnologies and traditional fluorescent materials. This technology affords real-time observation in situ of multiple biomarkers, allowing us to quantify their expression levels, and helping us to gain a deeper understanding of the interactions among biomolecules and the relationship between biomolecules and disease occurrence, progression, and prognosis. This has potential to aid in clinical diagnosis and treatment decision making.
关键词： Molecular imaging,Imaging,Biomarkers,Multicolor,Quantum dots
更新于2025-09-12 10:27:22
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Synthesis and evaluation of zirconium-89 labelled and long-lived GLP-1 receptor agonists for PET imaging
摘要： Introduction: Lately, zirconium-89 has shown great promise as a radionuclide for PET applications of long circulating biomolecules. Here, the design and synthesis of protracted and long-lived GLP-1 receptor agonists conjugated to desferrioxamine and labelled with zirconium-89 is presented with the purpose of studying their in vivo distribution by PET imaging. The labelled conjugates were evaluated and compared to a non-labelled GLP-1 receptor agonist in both in vitro and in vivo assays to certify that the modification did not significantly alter the peptides’ structure or function. Finally, the zirconium-89 labelled peptides were employed in PET imaging, providing visual verification of their in vivo biodistribution. Methods: The evaluation of the radiolabelled peptides and comparison to their non-labelled parent peptide was performed by in vitro assays measuring binding and agonistic potency to the GLP-1 receptor, physicochemical studies aiming at elucidating change in peptide structure upon bioconjugation and labelling as well as an in vivo food in-take study illustrating the compounds’ pharmacodynamic properties. The biodistribution of the labelled GLP-1 analogues was determined by ex vivo biodistribution and in vivo PET imaging. Results: The results indicate that it is surprisingly feasible to design and synthesize a protracted, zirconium-89 labelled GLP-1 receptor agonist without losing in vitro potency or affinity as compared to a non-labelled parent peptide. Physicochemical properties as well as pharmacodynamic properties are also maintained. The biodistribution in rats show high accumulation of radiolabelled peptide in well-perfused organs such as the liver, kidney, heart and lungs. The PET imaging study confirmed the findings from the biodistribution study with a significant high uptake in kidneys and presence of activity in liver, heart and larger blood vessels. Conclusions and Advances in Knowledge: This initial study indicates the potential to monitor the in vivo distribution of long-circulating incretin hormones using zirconium-89 based PET.
关键词： GLP-1,Bioconjugation,PET,Molecular imaging,Zirconium-89,Radiolabelling
更新于2025-09-12 10:27:22
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Cancer Theranostics || Multimodality Image-Guided Treatment
摘要： Recent advances in molecular biology and imaging technology with precision engineering have allowed in vivo imaging of anatomic structures at submillimeter ranges and pathologic processes at subnanomolar concentrations. Multimodality imaging is exemplified by the current practice of single photon emission computed tomography (SPECT-CT) and positron emission tomography computed tomography (PET-CT) [1]. Subcentimeter lesions on computed tomotraphy (CT) can be characterized by functional abnormalities identified on SPECT to enhance sensitivity of detecting radio-isotopes or PET, which routinely assess lesion glucose metabolism using F-18 FDG (fluorine-18 fluoro-2-fluorodeoxyglucose). Conversely, subcentimeter hypermetabolic lesions on SPECT or PET can be identified on CT to allow exact localization to guide various types of therapy including surgery, radiotherapy, and experimental therapies. Guided therapies target abnormal tissues, which often refer to, but are not limited to, neoplasms. For instance, drainage of an abdominal bacterial abcess may require scintigraphic confirmation of infection to determine the need of intervention and anatomic guidance from CT or magnetic resonance imaging (MRI) to access the lesion.
关键词： Cancer treatment,Radiotherapy,Multimodality imaging,PET-CT,SPECT-CT,Surgery,Image-guided therapy,Molecular imaging
更新于2025-09-10 09:29:36
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Polymethine Thiopyrylium Fluorophores with Absorption beyond 1000 nm for Biological Imaging in the Second Near-infrared Sub-window
摘要： Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by indocyanine green structure, a series of polymethine dyes with both absorption and emission in NIR-II window have been developed for NIR-II imaging, providing the feasibility to directly compare optical imaging in NIR-IIa (1300-1400 nm) sub-window under 1064 nm excitation with that in NIR-II window under 808 nm excitation. The signal-background ratio (SBR) and tumor to normal tissue ratio (T/NT) achieved great improvement under 1064 nm excitation in the imaging of mouse blood pool and U87 glioma tumors. Our study not only introduces a broadband emission fluorophore for both NIR-II and NIR-IIa imaging, but also reveals the advantages of NIR-II excitation over NIR-I in in vivo imaging.
关键词： Molecular imaging,U87MG glioma tumor,Polymethine thiopyrylium salts,Second near-infrared window
更新于2025-09-10 09:29:36
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High-energy direct photoelectron spectroscopy in strong-field ionization
摘要： Recently, in the tunneling regime of strong-field ionization an unexpected Coulomb field effect has been identified by numerical solution of the time-dependent Schr?dinger equation [Phys. Rev. Lett. 117, 243003 (2016)] in photoelectron spectra in the upper energy range of the direct electrons. We investigate the mechanism of the Coulomb effect employing a classical theory with Monte Carlo simulations of trajectories, and a quantum theory based on the generalized eikonal approximation for the continuum electron. The effect is shown to have a classical nature and is due to momentum space bunching of photoelectrons released not far from the peak of the laser field. Moreover, our analysis reveals specific features of the angular distribution of high-energy direct electrons, which can be employed for molecular imaging. For the H2+ molecule as an example we show the signatures of the molecule orientation and the molecular structure in the investigated angular distribution.
关键词： Coulomb field effect,generalized eikonal approximation,photoelectron spectra,strong-field ionization,molecular imaging
更新于2025-09-09 09:28:46
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Molecular Imaging: <i>In Vivo</i> Agents for the Diagnosis and Treatment of Cancer
摘要： Molecular imaging continues to advance the goal of improving diagnosis and treatment in cancer. This special issue examines a cross section of the current basic and clinical research across imaging modalities, probes, and molecular targets. The issue articles permit comparison of the advantages and limitations of varied modalities, including PET, SPECT, CT, MRI, ultrasound imaging, and fluorescence imaging. The corresponding agents in development are able to interact with many targets of relevance to cancer. Highly sensitive and specific in vivo agents permit visualization of receptor systems, enzymes, and proteins involved in cancer initiation, maintenance, and spread. As another dimension of cancer targeting, molecular probes for the tumor microenvironment, including stromal, endothelial, and immune cells, are increasingly recognized as key factors in attacking cancer. The caleidoscope of targets and methods available to achieve these goals is exemplified in this special issue. The topics cover the development of molecular imaging agents targeting the cholecystokinin 2 receptor (CCK2R), adenosine A3 receptor (A3R), and the human epidermal growth factor receptor 2 (HER2). Cancer stroma targeting is addressed with molecular probes for the vascular cell adhesion molecule 1 (VCAM-1) and endoglin (CD105), a proangiogenic growth factor, which are both overexpressed in a variety of malignancies. The tools used in the selection of displayed articles were intact molecules, small peptides, engineered proteins, antibodies and antibody fragments, nanoparticles, and targeting microbubbles, demonstrating the breadth of scaffolds currently to investigators and soon to cancer clinicians. Each paper included in this special issue approaches the challenge of molecular imaging in diagnosis and treatment of cancer in a different way, focusing on new molecules, innovative labelling strategies, and characterization in disease models. Each contribution stands on its own as a marker for the next advances in cancer understanding and patient care. The editors have endeavored to have the authors clearly point up the advantages of the current technologies and demonstrate the needs for advancement to the next stages of development. We hope this effort will stimulate the reader to think hard about their own research and how the community of cancer imaging investigators can continue progress from proof of concept to clinical use.
关键词： Cancer,Treatment,Diagnosis,In Vivo Agents,Molecular Imaging
更新于2025-09-09 09:28:46
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Activatable Near-Infrared Fluorescence Imaging Using PEGylated Bacteriochlorin-Based Chlorin and BODIPY-Dyads as Probes for Detecting Cancer
摘要： Near infrared (NIR) fluorescent probes are attractive tools for biomedical in vivo imaging due to the relatively deeper tissue penetration and lower background autofluorescence. Activatable probes are turned on only after binding to their target, further improving target to background ratios. However, the number of available activatable NIR probes is limited. In this study, we introduce two types of activatable NIR fluorophores derived from bacteriochlorin; chlorin-bacteriochlorin energy-transfer dyads and boron-dipyrromethene (BODIPY)-bacteriochlorin energy-transfer dyads. These fluorophores are characterized by multiple narrow excitation bands with relatively strong emission in the NIR. Targeted bacteriochlorin-based antibody or peptide probes have been previously limited by aggregation after conjugation. Polyethylene glycol (PEG) chains were added to improve the hydrophilicity without altering pharmacokinetics of the targeting moieties. These PEGylated bacteriochlorin-based activatable fluorophores have potential as targeted activatable, multi-color NIR fluorescent probes for in vivo applications.
关键词： Monoclonal antibody,Molecular imaging,Bacteriochlorin,Cancer
更新于2025-09-09 09:28:46