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Zwitterionic near-infrared fluorophore-conjugated epidermal growth factor for fast, real-time, and target-cell-specific cancer imaging
摘要： Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, which is associated with metastatic potential and poor prognosis in cancer patients. Therefore, development of EGFR-targeted sensitive imaging probes has been a challenge in tumor targeting, image-guided cancer surgery, patient-selective anti-EGFR therapy, and efficient targeted therapies. Methods: We synthesized a zwitterionic near-infrared fluorophore (ATTO655)-conjugated epidermal growth factor (EGF) as a novel activatable molecular probe. Fluorescence OFF/ON property and EGFR-targeting specificity of EGF-ATTO655 as well as its utility in real-time near-infrared (NIR) fluorescence imaging of EGFR-positive cancers were evaluated using in vitro and in vivo studies. Results: When conjugated to EGF, the fluorescence of ATTO655 quenched efficiently by photo-induced electron transfer (PET) mechanism between the conjugated dyes and nearby amino acid quenchers (tryptophan/tyrosine residues), which was stably maintained at physiological pH and in the presence of serum for at least 17 h. The fluorescence of EGF-ATTO655 turned on by receptor-mediated endocytosis and subsequent disintegration of EGF in EGFR-positive A431 cancer cells, thereby enabling specific and real-time fluorescence imaging of EGFR-positive cancer cells. Consequently, EGFR-positive tumors could be clearly visualized 3 h post-injection with a significantly high tumor-to-background ratio (TBR = 6.37). Conclusion: This PET mechanism-based OFF/ON type of EGF probe showed great potential for rapid, real-time, and target-cell-specific imaging of EGFR-overexpressing cancers in vitro and in vivo.
关键词： photo-induced electron transfer,Epidermal growth factor,real-time cancer imaging,tumor-specific targeting
更新于2025-11-21 11:24:58
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Plasmonic Gold Nanovesicles for Biomedical Applications
摘要： Gold nanoparticles (GNPs), with tunable optical properties, bioinertness, and surface multivalent effect, have been widely explored for biomedical applications. As one classical type of GNPs-based assemblies, plasmonic gold nanovesicles (GVs), with a hollow cavity, “solid skeleton” composed of GNPs cores and a “soft body” composed of functional polymers, have attracted considerable attention due to their tunable localized surface plasmon resonance, strong surface-enhanced Raman scattering properties, and high photothermal conversion efficiency. This review summarizes recent advances in biomedical applications for plasmonic GVs. Firstly, the synthesis methods of GVs are mainly including self-assembly and in situ gold growth methods. Secondly, the classification of GVs is described according to the morphology of GNPs cores. Thirdly, different biomedical applications of GVs are elaborated, including in vitro diagnosis, in vivo imaging, and in vivo therapy. Finally, the challenges and perspectives of GVs are discussed.
关键词： cancer therapy,drug delivery,gold nanovesicles,biodetection,cancer imaging
更新于2025-09-23 15:23:52
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Improved immuno-PET imaging of HER2-positive tumors in mice: Urokinase injection-triggered clearance enhancement of <sup>64</sup> Cu-trastuzumab
摘要： Immuno-positron emission tomography (immuno-PET) is expected to improve the specificity of small chemical tracers such as 18F-fluorodeoxyglucose. Whole antibodies significantly accumulate in target molecule-expressing tumors but frequently persist too long in the blood circulation for imaging purposes. We investigated the utility of whole antibodies, 64Cu-labeled via a urokinase-substrate linker, and their exogenous urokinase-responsive cleavage to enhance clearance of immuno-PET probes from the blood and shorten the time required to develop adequate imaging contrast. Specifically, we used 64Cu-labeled trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive tumor-bearing mice. 64Cu-labeled trastuzumab with a urokinase-cleavage site (64Cu-CB-TE1A1P-USL-trastuzumab) was synthesized using a bifunctional chelator incorporating a urokinase substrate peptide. Urokinase cleavage was analyzed in vitro by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and radio-gel permeation-high performance liquid chromatography. Improvements in radioisotope clearance and HER2-imaging by urokinase injection were evaluated by PET imaging and ex vivo biodistribution studies in A431 tumor-bearing mice. 64Cu-CB-TE1A1P-USL-trastuzumab was cleaved into smaller radioactive fragments by 20,000 IU/mL urokinase treatment in vitro at an efficacy of ~95%. The probe targeted HER2 in A431 tumors in mice within 24 h post-injection, and approximately two-thirds of the probe in the blood circulation was eliminated via renal clearance of radioactive fragments after three urokinase injections. Therefore, the tumor/blood ratio increased 3.0-fold. Without urokinase injection, the tumor accumulation of 64Cu-CB-TE1A1P-USL-trastuzumab slowly increased and the blood radioactivity decreased over 72 h. However, the tumor/blood ratios in mice after three urokinase injections were higher at 24 h than those in mice without injections at 72 h. The results indicate that our approach shortened the time required to develop adequate imaging contrast of immuno-PET by > 2 days. Therefore, this approach can benefit high-sensitivity imaging under lower radioactive decay conditions and can decrease patient radiation exposure. In addition, it could reduce other adverse effects of radioimmunotherapy.
关键词： immuno-positron emission tomography,cancer imaging,trastuzumab,urokinase,imaging contrast,clearance enhancement
更新于2025-09-23 15:23:52
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Special Section Guest Editorial: Quantitative Imaging and the Pioneering Efforts of Laurence P. Clarke
摘要： Quantitative imaging is growing in popularity and clinical utility, and this special section of the Journal of Medical Imaging features articles that present results of this method across medical imaging modalities and applications. Quantitative imaging is the science of extracting numeric information from images to measure or predict a patient’s health. Larry Clarke was an early and enthusiastic champion of quantitative methods in medical imaging, and the fullness and diversity of this issue stand as a tribute to his dedication to the field. Sadly, Larry passed away in April 2016 before many aspects of his vision for quantitative imaging could be realized.
关键词： National Cancer Institute,Cancer Imaging Program,Medical Imaging,Quantitative Imaging,Laurence P. Clarke
更新于2025-09-23 15:21:01
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Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging
摘要： Folic acid functionalized carbon quantum dot (FA-CQD) with ultrahigh quantum yield (50%) were synthesized by one-pot hydrothermal route using citric acid. The synthesized CQDs were characterized by fluorescence spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction. The cell viability of about 95% and 97% were obtained for MTT assay of the CQDs and FA-CQDs toward MCF-7 cells after 24 h of incubation respectively. The FA-CQDs were successfully applied for targeted imaging of cervical cancer (type HeLa) and human breast adenocarcinoma (type MCF7) cells using fluorescence microscope.
关键词： HeLa cancer cell,Ultra high quantum yield CQDs,MCF-7 cancer cell,Fluorescence imaging,Targeted cancer imaging
更新于2025-09-23 15:19:57
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Microwave-assisted ultra-fast synthesis of carbon quantum dots from linter: Fluorescence cancer imaging and human cell growth inhibition properties
摘要： The water dispersed-fluorescent carbon quantum dots (CDs) were synthesized using microwave-assisted hydrothermal process in the closed system from the waste cotton linter as a new carbon source. This method provided an ultra-fast, more effective, economical and easier synthesis for cancer-imaging applications compared to the other methods presented in literature. The morphological and optical properties of the hydrothermally produced carbon quantum dots were characterized by using FT-IR, transmission electron microscopy (TEM), SEM, EDX, UV–vis and fluorescent spectrophotometry techniques. An emission peak was observed at 420 nm when the CDs were excited at 376 nm. CDs were calculated to have an average particle diameter of 10.14 nm by TEM. In order to determine the usability of the CDs in cell imaging, two different concentrations (50 μL/mL and 100 μL/mL) of the CDs colloidal solution were applied to a human mesothelioma cell line, H2452, and human umbilical vein endothelial cells (HUVEC) for varying durations. While the fluorescent photos revealed that 2 h of exposure was sufficient for the cells to take the C-dots in and higher concentrations appeared brighter in the wavelengths studied (red channel (excitation/emission 586/646 nm), blue channel (390/446 nm) and the green channel (482/532 nm)), cell viability and proliferation assays indicated that the material was cytotoxic against the both cell lines and inhibited the cell growth in a time- and dose- dependent manner.
关键词： Fluorescence,Carbon dot,Cell inhibition,Cancer imaging,Microwave,Linter
更新于2025-09-23 15:19:57
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Cancer-Specific Biomarker hNQO1-Activatable Fluorescent Probe for Imaging Cancer Cells In Vitro and In Vivo
摘要： Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management. In the present study, we report a new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 activity in vitro and in vivo in both ratiometric and turn-on model. NQ-DCP was prepared by conjugating dicyanoisophorone fluoroprobe with hNQO1 activatable quinone propionic acid (QPA), which remain non-fluorescent until activation by tumor-specific hNQO1. NQ-DCP featured a large Stokes shift (145 nm), excellent biocompatibility, cell permeability, and selectivity towards hNQO1 allowed to differentiate cancer cells from healthy cells. We have successfully employed NQ-DCP to monitor non-invasive endogenous hNQO1 activity in brain tumor cells in vitro and in xenografted tumors developed in nude mice.
关键词： NAD(P)H quinone oxidoreductase 1,cancer biomarker,tumor diagnosis,fluorescent probe,cancer imaging,large Stokes shift,dicyanoisophorone
更新于2025-09-19 17:15:36
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Hybrid Nanostructures for Cancer Theranostics || Hybrid Nanostructures for In Vivo Imaging
摘要： Nanohybrids with well-defined optical properties and integrated functionalities are considered to be the most advanced next-generation blend of therapeutics and diagnostics: a simultaneous “theranostics”. Targeted delivery, real-time monitoring of administration, distribution, biotransformation, and elimination from the body are some of the beneficial attributes which have enabled it to get wide attention and acceptability. A spectrum of new-generation hybrid nanosystems for future biomedical applications has been fabricated, and has a variety of applications towards in vivo optical imaging, ultrasound (US) imaging, computed tomography (CT) of X-rays, magnetic resonance imaging (MRI), and positron emission tomography (PET). Multifunctional nanoparticles containing multiple contrast agents not only allow multimodal imaging but also improve the resolution of each of these imaging modalities. This chapter provides one of the most comprehensive detailed reports on the development of nanohybrids for cancer imaging to date.
关键词： Cancer imaging,Multimodal imaging,Theranostics,Contrast agents,Nanohybrids
更新于2025-09-10 09:29:36
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[Progress in Molecular Biology and Translational Science] Volume 160 || Fluorescent Proteins as Sensors for Cellular Behavior in Mice
摘要： Imaging of cancer cells in mice expressing fluorescent proteins has allowed the real-time tracing of cancer growth and metastasis and determination of efficacy of candidate antitumor and antimetastatic agents, especially in mouse orthotopic models. The use of fluorescent proteins to differentially label cancer cells in the nucleus and cytoplasm can visualize the nuclear–cytoplasmic dynamics of cancer cells in vivo, including mitosis, apoptosis, cell-cycle position, and differential behavior of nucleus and cytoplasm that occurs during cancer cell deformation, migration, and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases. Any in vivo process can be imaged using fluorescent proteins, allowing molecular biology to advance from in vitro studies to studying molecular processes in the living animal.
关键词： cancer imaging,metastasis,RFP,in vivo imaging,GFP,fluorescent proteins
更新于2025-09-10 09:29:36
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Logic Sensing of MicroRNA in Living Cells Using DNA-Programmed Nanoparticle Network with High Signal Gain
摘要： Molecular circuits capable of implementing Boolean logic in cellular environments have emerged as an important tool for in situ sensing, elucidating, and modulating cell functions. The performance of existing molecular computation devices in living cells is limited because of the low level of biomolecular inputs and moderate signal gain. Herein, we devised a new class of DNA-programmed nanoparticle network with integrated molecular computation and signal amplification functions for logic sensing of dual microRNA (miRNA) molecules in living cells. The nanoparticle network, which is composed of DNA-bridged gold nanoparticles and quantum dots (QDs), could simultaneously interface with two miRNA molecules, amplify the molecular inputs, perform a calculation through AND logic gate, and generate QD photoluminescence (PL) as an output signal. Significant improvement in imaging sensitivity is achieved by integrating the signal amplifier into the molecular computation device. It allows discrimination of specific cancer cell type via intelligent sensing of miRNA patterns in living cells.
关键词： assembly,microRNA,DNA,cancer imaging,gold nanoparticle,logic gate,quantum dot
更新于2025-09-09 09:28:46