Dedicated to the memory of Professor Briton Chance on the ccasion of his 100th birthday(July24 th,2013),and remembering mary erciting discussions on the orygenation of breast cancer,ontumor hyporia in general and imag...Dedicated to the memory of Professor Briton Chance on the ccasion of his 100th birthday(July24 th,2013),and remembering mary erciting discussions on the orygenation of breast cancer,ontumor hyporia in general and imaging of the orygenation status of malignant tumors.Hypoxic tissue subvolumes are a hallmark feat ure of solid malignant tumors,relevant for cancertherapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resist ance to several commonly used anticancer strategies.Pathogenetic mech-anisms leading to hypoxia are diverse,may coexist within the same tumor and are commonlygrouped according to the duration of their ffects.Chronic hypoxia is mainly caused by difusionlimitations resulting from enlarged intercapilary distances and adverse difusion geometriesand--to a lsser extent--by hypoxemia,compromised perfusion or long-lasting microregionalfow stops.Conversely,acute hypoxia preferentilly results from transient disruptions in per.fusion.While each of these features of the tumor microenvironment can contribute to a criticalreduction of oxy gen availability,the delivery of imaging agents(as well as nutrients and anti-cancer agents)may be compromised or remain unaffected,Thus,a critial appraisal of the ffectsof the various mechanisms leading to hypoxia with regard to the blood-bome delivery of imagingagents is necessary to judge their ability to correctly represent the hypoxic phenotype of solidmalignancies.展开更多
Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking c...Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles(NPs), especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs' size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer(Lb L) capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin(T2) relaxivity and convenience for further functionalization.展开更多
Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and ...Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer cases.Despite the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed countries.The C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and cells.CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and angiogenesis.In addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells.Studies have shown that CXCL12 and its receptor,CXCR4,are highly expressed in ESCC.This abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening prognosis.At present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors.This article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC.Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.展开更多
Meisoindigotin has been demonstrated as a new type of cancer chemotherapeutic agent.N-^(11)C-meisoindigotin was synthesized by N-^(11)C-methyIation of the isoindigotin precursor with ^(11)C-labelled methyl trifl...Meisoindigotin has been demonstrated as a new type of cancer chemotherapeutic agent.N-^(11)C-meisoindigotin was synthesized by N-^(11)C-methyIation of the isoindigotin precursor with ^(11)C-labelled methyl triflate.The decay corrected radiochemical yields were 15-25%,and the specific radioactivity was 1.0-1.2 Ci/μmol at the end of synthesis.The cellular uptake of[N-^(11)C]-meisoindigotin was evaluated in four different lung cancer cell lines.Our results showed that the A549,GLC-82,95D cell lines exhibited higher uptake than 95C cell line after incubation for 60 min.N-^(11)-meisoindigotin was a promising candidate for further development as a novel PET radiotracer for imaging of cyclin-dependent kinases(CDKs) and GSK-3β.展开更多
Comprehensive Summary,Stimuli-controlled disassembly process has shown promise to direct delivery of probes and/or spatial-temporally control imaging signals for molecular imaging in vivo.Via the disassembly process,w...Comprehensive Summary,Stimuli-controlled disassembly process has shown promise to direct delivery of probes and/or spatial-temporally control imaging signals for molecular imaging in vivo.Via the disassembly process,well defined nanoprobes with a stimulus-responsive moiety can be controllably converted into small-molecular imaging agents in response to a stimulus,leading to a switch in imaging signals.Moreover,the on-site released small-molecule probes could enhance penetration into the deep tissue for improved imaging of deep-seated molecular targets.Therefore,such a stimuli-controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects.In this review article,we first briefly introduce the general principle of stimuli-controlled disassembly.We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process.Activatable probes by using multiple stimuli to control cascaded in situ self-assembly and disassembly processes are also discussed.Finally,we close with a conclusion of current challenges and perspective in this field.展开更多
Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the selfhealing ability and lead to joint dysfunction.However,the low longitudinal T1 relaxivity(r1)and non-s...Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the selfhealing ability and lead to joint dysfunction.However,the low longitudinal T1 relaxivity(r1)and non-specificity of contrast agents(such as gadolinium(III)-diethylenetriamine-pentaacetic acid(Gd-DTPA))significantly limit the efficiency of clinical magnetic resonance imaging(MRI)applications.To overcome these drawbacks,we integrated hyaluronic acid(HA)with Gd to synthesize a Gd-DTPA-HA composite,which was subsequently freeze-dried to produce nanoparticles(NPs).The resultant Gd-HA NPs demonstrated a greater r1 value(12.51 mM^-1 s^-1)compared with the bulk Gd-DTPA-HA(8.37 mM^-1 s^-1)and clinically used Gd-DTPA(3.88 mM^-1 s^-1).Moreover,the high affinity of HA to the cartilage allowed these NPs to penetrate deeper beyond the cartilage surface.As a result,Gd-HA NPs considerably increased the quality of cartilage and lesion MR images via their intra-articular injection in vivo.Specifically,2 h after NP administration,the signal-to-noise ratio at the injured cartilage site was 2.3 times greater than the value measured before the injection.In addition,Gd-HA NPs exhibited good biosafety properties due to the absence of adverse effects in the blood or on the main organs.It was also showed that Gd NPs were first metabolized by the kidney and liver and then excreted from the body with urine.Thus,Gd-HA NPs can potentially serve as an efficient MRI contrast agent for improved detection of cartilage injuries.展开更多
As a hybrid imaging technique, photoacoustic imaging (PAI) can provide multiscale morphological information of tissues, and the use of multi-spectral PAI (MSPAI) can recover the spatial distribution of chromophore...As a hybrid imaging technique, photoacoustic imaging (PAI) can provide multiscale morphological information of tissues, and the use of multi-spectral PAI (MSPAI) can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots (Pdots) that show broad and strong optical absorption in the visible-light region (500-700 nm). The performances of gold nanoparticles (GNPs) and gold nanorods (GNRs), which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.展开更多
Objective To evaluate the clinical value of myocardial perfusion imaging with dual-source dual-energy CT and a contrast agent at a low concentration in the diagnosis of myocardial infarction in the elderly.Methods One...Objective To evaluate the clinical value of myocardial perfusion imaging with dual-source dual-energy CT and a contrast agent at a low concentration in the diagnosis of myocardial infarction in the elderly.Methods Onestop cardiac imaging with dual-source CT was conducted in 138 elderly patients diagnosed with myocardial infarction between October 2015 and May 2016.The展开更多
A nitrone-modified 1,8-naphthalimide was desig ned as a novel bioorthog on alactivated turn-on probe based on strain-promoted alkyne-nitrone cycloadditio n(SPANC).The bioorthog onal cycloadducts were subseque ntly tra...A nitrone-modified 1,8-naphthalimide was desig ned as a novel bioorthog on alactivated turn-on probe based on strain-promoted alkyne-nitrone cycloadditio n(SPANC).The bioorthog onal cycloadducts were subseque ntly tran sformed into fluoresce nt rearra nge-ment products by photo-accelerati on,which exhibited sign ificant fluoresce nee enhan ceme nt,large stokes shift,and high fluores-cence qua ntum yield.DFT calculati ons were performed to elucidate the fluoresce nee OFF-ON mecha nism.This fluoroge nic strategy was successfully applied to labeling of proteins and visualizing mitochondria in live cells in real time.展开更多
Two types of ligands-biphenyl and stilbene derivatives, -which can be labeled with Tc-99m for the diagnosis of Alzheimer' s disease (AD) have been synthesized successfully. The key steps in these two syntheses inv...Two types of ligands-biphenyl and stilbene derivatives, -which can be labeled with Tc-99m for the diagnosis of Alzheimer' s disease (AD) have been synthesized successfully. The key steps in these two syntheses involved Suzuki reaction and Wittig reaction respectively. The new discovered debromination reaction may be expanded to the compounds with double or triple bond adjacent to the carbon atom bearing the bromine atoms. These types of syntheses provide a route to a series of biphenyl and stilbene derivatives that will benefit the search of new imaging agents for AD.展开更多
Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury (TBI). Non-invasive imaging of the affected tissue is a key component of novel the...Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury (TBI). Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs), encapsulating both near infrared (NIR) fluorophores and perfluorocarbons (PFCs), were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging (^19F MRI) using newly designed PLGA NP(NIR700 + PFC)-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.展开更多
Theranostic nanoagents that integrate the diagnoses and therapies within a single nanomaterial are compelling in their use for highly precise and efficient antitumor treatments. Herein, polyethylene glycol (PEG)-mod...Theranostic nanoagents that integrate the diagnoses and therapies within a single nanomaterial are compelling in their use for highly precise and efficient antitumor treatments. Herein, polyethylene glycol (PEG)-modified cobalt sulfide nanosheets (CoS-PEG NSs) are synthesized and unitized as a powerful theranostic nanoagent for efficient photothermal conversion and multimodal imaging for the first time. We demonstrate that the obtained CoS-PEG NSs show excellent compatibility and stability in water and various physiological solutions, and can be effectively inter- nalized by cells, but exhibit a low cytotoxicity. The CoS-PEG NSs exhibit an efficient photothermal conversion capacity, benefited from the strong near-infrared (NIR) absorption, high photothermal conversion efficiency (~ 33.0%), and excellent photo- thermal stability. Irnportant136 the highly effective photothermal killing effect on cancer ceils after exposure to CoS-PEG NSs plus laser irradiation has been con- firmed by both the standard Cell Counting Kit-8 and live-dead cell staining assays, revealing a concentration-dependent photothermal therapeutic effect. Moreover, utilizing the strong NIR absorbance together with the T2-MR contrast ability of the CoS-PEG NSs, a high-contrast triple-modal imaging, i.e., photoacoustic (PA), infrared thermal (IRT), and magnetic resonance (MR) imaging, can be achieved, suggesting a great potential for multimodal imaging to provide comprehensive cancer diagnosis. Our work introduces the first bioapplication of the CoS-PEG nanomaterial as a potential theranostic nanoplatform and may promote further rational design of CoS-based nanostructures for precise/effident cancer diagnosis and therapy.展开更多
A simple and straightforward strategy for magnetic resonance imaging (MRI) of stem cell transplants in terms of their viability, migration and homing, and differentiation has been pursued over the years. Herein we c...A simple and straightforward strategy for magnetic resonance imaging (MRI) of stem cell transplants in terms of their viability, migration and homing, and differentiation has been pursued over the years. Herein we couple Gd-DOTA with triphenylphosphonium (TPP) to yield small molecule (Gd-DOTA)i-TPP (i = 1,4) agents and show that labeling cells with (Gd-DOTA)i-TPP via electro- poration (EP) results in two distinct cellular distributions of (Gd-DOTA)i-TPP: freely and evenly distributed in the cytosol or cell-assembled nanoclusters in the cytoplasm. The two distinct cellular distributions contribute in different ways to MRI signals in vitro and in vivo. Importantly, we present a detailed interpretation of MRI results based on the signal intensity equation and cellular longitudinal (T1-) and transverse (Ta-) relaxation rates of water protons. We demonstrate that cell-assembled (Gd-DOTA)i-TPP nanoclusters not only promote its intracellular retention time but also induce significant MRI signal reduction, which act as an excellent T2 contrast agent and allows for unambiguous reporting of in vivo viability and migration of cell transplants under T2-weighted MRI over a long period. Notably,(Gd-DOTA)i-TPP agents released as a result of exocytosis or cell death induce signal enhancement in the surrounding tissue such that the labeled cells can be unambiguously discriminated from its host tissue. The labeling and imaging strategy provides abundant information on the in vivo fates of stem cell transplants. The strategy features a single contrast, single imaging mode with dual signal output.展开更多
In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed t...In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents (CAs) available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells (RBCs) as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.展开更多
In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles...In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles have a core-shell structure and a narrow size distribution in the range of 261±27 nm.The fluorescent properties of the prepared C@Gd_(2)O_(3)particles were accessed by a room-temperature photoluminescence study,while the longitudinal relaxivity(r1)was examined by using a clinical 1.5 T MRI scanner.A murine fibroblast L-929 cell line was used to examine the cytotoxicity and capability of the prepared C@Gd_(2)O_(3)particles for the fluorescent labeling.The obtained results show that the prepared C@Gd_(2)O_(3)particles could be used as a dual-mode contrast agent for magnetic resonance and fluorescence imaging.展开更多
Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,pr...Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,proteins,mRNAs,non-coding RNAs,and DNAs,and disseminating long-distance intercellular communications in various biological processes.Among various cell-line or biological fluid derived exosomes,milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications.To be an effective delivery carrier for their clinical translation,exosomes must inbuilt loading,release,targeting,and imaging/tracking characteristics.Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging applications.This review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery approaches.It is emphasized on possible modifications of exosomes towards increasing the stability and delivery of agents.This article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.展开更多
Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-bas...Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-based fluorescence probe NP-FA with superb blood-brain barrier permeable abilities was exquisitely designed.The probe responded to FA with significant fluorescence increases(F/F0=81),thus laying the foundation for the sensitive detection of FA in cuvette and in vivo.Moreover,the probe also possessed some fasci-nating performances,including endoplasmic reticulum(ER)-targeting abilities,good one-photon/two-photon absorption properties,and appropriate hydrophobicity property(log P=2.34±0.05).As a result,the probe can readily reflect the overproduction of FA con-tent in live cells under ER stress by high-fidelity two-photon imaging.More interestingly,ex vivo imaging of AD brains and two-photon imaging of AD slice tissues visually disclosed that the FA level of AD brain is much higher than that of the normal brain.This work afforded a specific activity-based probe for the imaging of FA in the AD mouse brains,which could be further extended to FA-related studies in Alzheimer's disease.展开更多
Since the advent of fluorescent probes,they have been widely used in the field of life sciences.Fluorescent probes can not only light up the cells,tissues and organs,but also be used to explore the bio-distribution of...Since the advent of fluorescent probes,they have been widely used in the field of life sciences.Fluorescent probes can not only light up the cells,tissues and organs,but also be used to explore the bio-distribution of specific types of disease markers.Therefore,the development of new fluorescent probes capable of recognition of bio-markers is extremely important for the diagnosis of the related diseases.Herein,we focus on our recent works experienced the evolution from the beginning of simply fluorescent probes to the construction of theranostics platform.We have developed a series of new fluorescent probes for the detecting and imaging of reactive oxygen species(ROS)and specific enzymes in vitro and in living cells.With the shift of the fluorescence signal from visible to near-infrared region,we expanded the application of the fluorescent probes from in vitro to in vivo.Very recently,we further constructed theranostics platforms to combine the diagnosis immediately with the corresponding treatment.展开更多
文摘Dedicated to the memory of Professor Briton Chance on the ccasion of his 100th birthday(July24 th,2013),and remembering mary erciting discussions on the orygenation of breast cancer,ontumor hyporia in general and imaging of the orygenation status of malignant tumors.Hypoxic tissue subvolumes are a hallmark feat ure of solid malignant tumors,relevant for cancertherapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resist ance to several commonly used anticancer strategies.Pathogenetic mech-anisms leading to hypoxia are diverse,may coexist within the same tumor and are commonlygrouped according to the duration of their ffects.Chronic hypoxia is mainly caused by difusionlimitations resulting from enlarged intercapilary distances and adverse difusion geometriesand--to a lsser extent--by hypoxemia,compromised perfusion or long-lasting microregionalfow stops.Conversely,acute hypoxia preferentilly results from transient disruptions in per.fusion.While each of these features of the tumor microenvironment can contribute to a criticalreduction of oxy gen availability,the delivery of imaging agents(as well as nutrients and anti-cancer agents)may be compromised or remain unaffected,Thus,a critial appraisal of the ffectsof the various mechanisms leading to hypoxia with regard to the blood-bome delivery of imagingagents is necessary to judge their ability to correctly represent the hypoxic phenotype of solidmalignancies.
基金Project supported by the National Key Basic Research Program of China(Grant No.2013CB933903)the National Natural Science Foundation of China(Grant Nos.20974065+2 种基金51173117and 50830107)the Scientific Research Start-up Fund of Kunming University of Science and Technology(Grant No.KKSY201305089)
文摘Recent progress of the preparation and applications of superparamagnetic iron oxide(SPIO) clusters as magnetic resonance imaging(MRI) probes is reviewed with regard to their applications in labeling and tracking cells in vivo, in diagnosis of cardiovascular diseases and tumors, and in drug delivery systems. Magnetic nanoparticles(NPs), especially SPIO nanoparticles, have long been used as MRI contrast agents and as an advantageous nanoplatform for drug delivery,taking advantage of their unique magnetic properties and ability to function at the molecular and cellular levels. Due to advances in nanotechnology, various means to control SPIO NPs' size, composition, magnetization and relaxivity have been developed, as well as ways to usefully modify their surface. Recently, self-assembly of SPIO NP clusters in particulate carriers — such as polymeric micelles, vesicles, liposomes, and layer-by-layer(Lb L) capsules — have been widely studied for application as ultrasensitive MRI probes, owing to their remarkably high spin–spin(T2) relaxivity and convenience for further functionalization.
基金supported by the National Natural Science Foundation of China(Grant Nos.81772619 and 81702405)Wu Jieping Medical Foundation(Grant No.320.6750.17519)+1 种基金Bethune Charitable Foundation(Grant No.HZB-20190528-18)Tianjin Natural Science Foundation for Youth(Grant No.19JCQNJC10800)。
文摘Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer cases.Despite the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed countries.The C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and cells.CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and angiogenesis.In addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells.Studies have shown that CXCL12 and its receptor,CXCR4,are highly expressed in ESCC.This abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening prognosis.At present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors.This article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC.Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.
基金supported by grants from the National Natural Science Foundation of China(No81071170)
文摘Meisoindigotin has been demonstrated as a new type of cancer chemotherapeutic agent.N-^(11)C-meisoindigotin was synthesized by N-^(11)C-methyIation of the isoindigotin precursor with ^(11)C-labelled methyl triflate.The decay corrected radiochemical yields were 15-25%,and the specific radioactivity was 1.0-1.2 Ci/μmol at the end of synthesis.The cellular uptake of[N-^(11)C]-meisoindigotin was evaluated in four different lung cancer cell lines.Our results showed that the A549,GLC-82,95D cell lines exhibited higher uptake than 95C cell line after incubation for 60 min.N-^(11)-meisoindigotin was a promising candidate for further development as a novel PET radiotracer for imaging of cyclin-dependent kinases(CDKs) and GSK-3β.
基金the National Natural Science Foundation of China(22137003 and 21922406)Natural Science Foundation of Jiangsu Province(BK20200301 and BK20190055)the Fundamental Research Funds for the Central Universities(020514380251)are acknowledged.
文摘Comprehensive Summary,Stimuli-controlled disassembly process has shown promise to direct delivery of probes and/or spatial-temporally control imaging signals for molecular imaging in vivo.Via the disassembly process,well defined nanoprobes with a stimulus-responsive moiety can be controllably converted into small-molecular imaging agents in response to a stimulus,leading to a switch in imaging signals.Moreover,the on-site released small-molecule probes could enhance penetration into the deep tissue for improved imaging of deep-seated molecular targets.Therefore,such a stimuli-controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects.In this review article,we first briefly introduce the general principle of stimuli-controlled disassembly.We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process.Activatable probes by using multiple stimuli to control cascaded in situ self-assembly and disassembly processes are also discussed.Finally,we close with a conclusion of current challenges and perspective in this field.
基金supported by the National Natural Science Foundation of China(81671652,81902198)National Key Research and Development Program of China(2018YFC2000205)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2020A1515010398)China Postdoctoral Science Foundation(BX20190150,2019M662980)President Foundation of Zhujiang Hospital,Southern Medical University(yzjj2018rc09)Scientific Research Foundation of Southern Medical University(C1051353,PY2018N060).
文摘Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the selfhealing ability and lead to joint dysfunction.However,the low longitudinal T1 relaxivity(r1)and non-specificity of contrast agents(such as gadolinium(III)-diethylenetriamine-pentaacetic acid(Gd-DTPA))significantly limit the efficiency of clinical magnetic resonance imaging(MRI)applications.To overcome these drawbacks,we integrated hyaluronic acid(HA)with Gd to synthesize a Gd-DTPA-HA composite,which was subsequently freeze-dried to produce nanoparticles(NPs).The resultant Gd-HA NPs demonstrated a greater r1 value(12.51 mM^-1 s^-1)compared with the bulk Gd-DTPA-HA(8.37 mM^-1 s^-1)and clinically used Gd-DTPA(3.88 mM^-1 s^-1).Moreover,the high affinity of HA to the cartilage allowed these NPs to penetrate deeper beyond the cartilage surface.As a result,Gd-HA NPs considerably increased the quality of cartilage and lesion MR images via their intra-articular injection in vivo.Specifically,2 h after NP administration,the signal-to-noise ratio at the injured cartilage site was 2.3 times greater than the value measured before the injection.In addition,Gd-HA NPs exhibited good biosafety properties due to the absence of adverse effects in the blood or on the main organs.It was also showed that Gd NPs were first metabolized by the kidney and liver and then excreted from the body with urine.Thus,Gd-HA NPs can potentially serve as an efficient MRI contrast agent for improved detection of cartilage injuries.
基金Acknowledgements This study was supported by the University of Macao in Macao (Nos. MYRG2014-00093-FHS, MYRG 2015-00036-FHS, and MYRG2016-00110-FHS), Macao government (Nos. FDCT 026/2014/A1 and FDCT 025/2015/A1), and the National Natural Science Foundation of China (No. 11434017).
文摘As a hybrid imaging technique, photoacoustic imaging (PAI) can provide multiscale morphological information of tissues, and the use of multi-spectral PAI (MSPAI) can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots (Pdots) that show broad and strong optical absorption in the visible-light region (500-700 nm). The performances of gold nanoparticles (GNPs) and gold nanorods (GNRs), which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.
文摘Objective To evaluate the clinical value of myocardial perfusion imaging with dual-source dual-energy CT and a contrast agent at a low concentration in the diagnosis of myocardial infarction in the elderly.Methods Onestop cardiac imaging with dual-source CT was conducted in 138 elderly patients diagnosed with myocardial infarction between October 2015 and May 2016.The
基金This work was supported by the Beijing Nova Program(Z201100006820049)the National Natural Science Foundation of China(No.21907109).
文摘A nitrone-modified 1,8-naphthalimide was desig ned as a novel bioorthog on alactivated turn-on probe based on strain-promoted alkyne-nitrone cycloadditio n(SPANC).The bioorthog onal cycloadducts were subseque ntly tran sformed into fluoresce nt rearra nge-ment products by photo-accelerati on,which exhibited sign ificant fluoresce nee enhan ceme nt,large stokes shift,and high fluores-cence qua ntum yield.DFT calculati ons were performed to elucidate the fluoresce nee OFF-ON mecha nism.This fluoroge nic strategy was successfully applied to labeling of proteins and visualizing mitochondria in live cells in real time.
基金Project supported by the National Institute of Health(NIH)USA and the Institute for the Study of Aging(ISOA)USA.
文摘Two types of ligands-biphenyl and stilbene derivatives, -which can be labeled with Tc-99m for the diagnosis of Alzheimer' s disease (AD) have been synthesized successfully. The key steps in these two syntheses involved Suzuki reaction and Wittig reaction respectively. The new discovered debromination reaction may be expanded to the compounds with double or triple bond adjacent to the carbon atom bearing the bromine atoms. These types of syntheses provide a route to a series of biphenyl and stilbene derivatives that will benefit the search of new imaging agents for AD.
文摘Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury (TBI). Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs), encapsulating both near infrared (NIR) fluorophores and perfluorocarbons (PFCs), were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging (^19F MRI) using newly designed PLGA NP(NIR700 + PFC)-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.
基金This work was financially supported by the National Natural Science Foundation of China (NSFC) (Nos. 21473045 and 51401066), the Fundamental Research Funds from the Central University (PIRSOF HIT A201503), and the State Key Laboratory of Urban Water Resource and Environment, the Harbin Institute of Technology (No. 2018DX04).
文摘Theranostic nanoagents that integrate the diagnoses and therapies within a single nanomaterial are compelling in their use for highly precise and efficient antitumor treatments. Herein, polyethylene glycol (PEG)-modified cobalt sulfide nanosheets (CoS-PEG NSs) are synthesized and unitized as a powerful theranostic nanoagent for efficient photothermal conversion and multimodal imaging for the first time. We demonstrate that the obtained CoS-PEG NSs show excellent compatibility and stability in water and various physiological solutions, and can be effectively inter- nalized by cells, but exhibit a low cytotoxicity. The CoS-PEG NSs exhibit an efficient photothermal conversion capacity, benefited from the strong near-infrared (NIR) absorption, high photothermal conversion efficiency (~ 33.0%), and excellent photo- thermal stability. Irnportant136 the highly effective photothermal killing effect on cancer ceils after exposure to CoS-PEG NSs plus laser irradiation has been con- firmed by both the standard Cell Counting Kit-8 and live-dead cell staining assays, revealing a concentration-dependent photothermal therapeutic effect. Moreover, utilizing the strong NIR absorbance together with the T2-MR contrast ability of the CoS-PEG NSs, a high-contrast triple-modal imaging, i.e., photoacoustic (PA), infrared thermal (IRT), and magnetic resonance (MR) imaging, can be achieved, suggesting a great potential for multimodal imaging to provide comprehensive cancer diagnosis. Our work introduces the first bioapplication of the CoS-PEG nanomaterial as a potential theranostic nanoplatform and may promote further rational design of CoS-based nanostructures for precise/effident cancer diagnosis and therapy.
基金This work was funded by general projects from the National Natural Science Foundation of China (Nos. 21673281 and 31371010), a Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA01030203), and a Basic Research Project from the Ministry of Science and Technology of China (No. 2011CB965004). The authors also acknowledge Karebay Biochem Inc. for assistance with synthesis of DOTArTPP.
文摘A simple and straightforward strategy for magnetic resonance imaging (MRI) of stem cell transplants in terms of their viability, migration and homing, and differentiation has been pursued over the years. Herein we couple Gd-DOTA with triphenylphosphonium (TPP) to yield small molecule (Gd-DOTA)i-TPP (i = 1,4) agents and show that labeling cells with (Gd-DOTA)i-TPP via electro- poration (EP) results in two distinct cellular distributions of (Gd-DOTA)i-TPP: freely and evenly distributed in the cytosol or cell-assembled nanoclusters in the cytoplasm. The two distinct cellular distributions contribute in different ways to MRI signals in vitro and in vivo. Importantly, we present a detailed interpretation of MRI results based on the signal intensity equation and cellular longitudinal (T1-) and transverse (Ta-) relaxation rates of water protons. We demonstrate that cell-assembled (Gd-DOTA)i-TPP nanoclusters not only promote its intracellular retention time but also induce significant MRI signal reduction, which act as an excellent T2 contrast agent and allows for unambiguous reporting of in vivo viability and migration of cell transplants under T2-weighted MRI over a long period. Notably,(Gd-DOTA)i-TPP agents released as a result of exocytosis or cell death induce signal enhancement in the surrounding tissue such that the labeled cells can be unambiguously discriminated from its host tissue. The labeling and imaging strategy provides abundant information on the in vivo fates of stem cell transplants. The strategy features a single contrast, single imaging mode with dual signal output.
文摘In medicine, discrimination between pathologies and normal areas is of great importance, and in most cases, such discrimination is made possible by novel imaging technologies. Numerous modalities have been developed to visualize tissue vascularization in cardiovascular diseases or during angiogenic and vasculogenic processes. Here, we report the recent advances in vasculature imaging, providing an overview of the current non-invasive approaches in biomedical diagnostics and potential future strategies for prognostic assessment of vessel diseases, such as aneurysms and coronary artery occlusion leading to myocardial infarction. There are several contrast agents (CAs) available to improve the visibility of specific tissues at the early stage of diseases, allowing for rapid treatment. However, CAs are also hampered by numerous limitations, including rapid diffusion from blood vessels into the interstitial space, toxicity, and low sensitivity. Extravasation from blood vessels leads to a rapid loss of the image. If the contrast medium can fully be confined to the vascular space, high-resolution structural and functional vascular imaging could be obtained. Many scientists have contributed new materials and/or new carrier systems. For example, the use of red blood cells (RBCs) as CA-delivery systems appears to provide a scalable alternative to current procedures that allows adequate vascular imaging. Recognition and removal of CAs from the circulation can be prevented and/or delayed by using RBCs as biomimetic CA-carriers, and this technology should be clinically validated.
基金supported by the 2014 Post-Doc,Development Program of Pusan National Universitysupported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(No.2014R1A2A1A11051146).
文摘In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles have a core-shell structure and a narrow size distribution in the range of 261±27 nm.The fluorescent properties of the prepared C@Gd_(2)O_(3)particles were accessed by a room-temperature photoluminescence study,while the longitudinal relaxivity(r1)was examined by using a clinical 1.5 T MRI scanner.A murine fibroblast L-929 cell line was used to examine the cytotoxicity and capability of the prepared C@Gd_(2)O_(3)particles for the fluorescent labeling.The obtained results show that the prepared C@Gd_(2)O_(3)particles could be used as a dual-mode contrast agent for magnetic resonance and fluorescence imaging.
基金support from Department of Immunology and Microbiology,School of Medicine,University of Texas Rio Grande Valley to MMY,MJ,and SCC.This work is partially supported by NIH grants(R01 CA210192,R01 CA206069 and R01 CA204552).
文摘Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles.Exosomes have proven to be excellent nanocarriers for carrying lipids,proteins,mRNAs,non-coding RNAs,and DNAs,and disseminating long-distance intercellular communications in various biological processes.Among various cell-line or biological fluid derived exosomes,milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications.To be an effective delivery carrier for their clinical translation,exosomes must inbuilt loading,release,targeting,and imaging/tracking characteristics.Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging applications.This review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery approaches.It is emphasized on possible modifications of exosomes towards increasing the stability and delivery of agents.This article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.
基金the National Natural Science Foundation of China(Nos.22174034,21804033,and 21625503)the Natural Science Foundation of Hubei Province(2021CFB305)。
文摘Formaldehyde(FA)plays critical roles in Alzheimer's disease and the associations between FA and Alzheimer's disease(AD)are still obscure.To reveal FA fluxes in the Alzheimer's disease brain,an activity-based fluorescence probe NP-FA with superb blood-brain barrier permeable abilities was exquisitely designed.The probe responded to FA with significant fluorescence increases(F/F0=81),thus laying the foundation for the sensitive detection of FA in cuvette and in vivo.Moreover,the probe also possessed some fasci-nating performances,including endoplasmic reticulum(ER)-targeting abilities,good one-photon/two-photon absorption properties,and appropriate hydrophobicity property(log P=2.34±0.05).As a result,the probe can readily reflect the overproduction of FA con-tent in live cells under ER stress by high-fidelity two-photon imaging.More interestingly,ex vivo imaging of AD brains and two-photon imaging of AD slice tissues visually disclosed that the FA level of AD brain is much higher than that of the normal brain.This work afforded a specific activity-based probe for the imaging of FA in the AD mouse brains,which could be further extended to FA-related studies in Alzheimer's disease.
基金the financial support from the Fundamental Research Funds for the Central Universities(2232021A-06)the National Natural Science Foundation of China(21877013,22007012,22177019)the Shanghai Sailing Program(20YF1401100).
文摘Since the advent of fluorescent probes,they have been widely used in the field of life sciences.Fluorescent probes can not only light up the cells,tissues and organs,but also be used to explore the bio-distribution of specific types of disease markers.Therefore,the development of new fluorescent probes capable of recognition of bio-markers is extremely important for the diagnosis of the related diseases.Herein,we focus on our recent works experienced the evolution from the beginning of simply fluorescent probes to the construction of theranostics platform.We have developed a series of new fluorescent probes for the detecting and imaging of reactive oxygen species(ROS)and specific enzymes in vitro and in living cells.With the shift of the fluorescence signal from visible to near-infrared region,we expanded the application of the fluorescent probes from in vitro to in vivo.Very recently,we further constructed theranostics platforms to combine the diagnosis immediately with the corresponding treatment.