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
Considering the development of magnetic resonance imaging (MRI) under ultrahigh magnetic field (〉3 T), the exploration of novel contrast agents (CAs) for ultrahigh field MRI is urgently needed. Herein, we repor...Considering the development of magnetic resonance imaging (MRI) under ultrahigh magnetic field (〉3 T), the exploration of novel contrast agents (CAs) for ultrahigh field MRI is urgently needed. Herein, we report polyethyleneimine (PEI)-coated TbF3 nanoparticles (NPs), which were synthesized by a facile solvothermal method, as potential dual-mode CAs for ultrahigh field MRI and X-ray computed tomography (CT). Owing to their strong paramagnetism, the TbF3 NPs showed excellent transverse relaxivity (395.77 mM-l.s-1) and negligible longitudinal relaxivity under an ultrahigh magnetic field (7 T) with a great potential as a T2-weighted MRI contrast agent. Furthermore, by comparison with the clinically used CT CAs (iohexol), the TbF3 NPs showed superior X-ray attenuation ability. The practical application for T2-weighted MRI and CT imaging was demonstrated with an animal model. Moreover, cell cytotoxicity and in vivo toxicity assessments implied the low toxicity of TbF3 NPs. In summary the above results indicate that TbF3 NPs are promising candidates for ultrahigh field MRI and CT dual-mode imaging.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
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
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This work was supported by the National Natural Science Foundation of China (No. 21425101, 21371011, and 21321001) and the National Basic Research Program of China (No. 2014CB643800).
文摘Considering the development of magnetic resonance imaging (MRI) under ultrahigh magnetic field (〉3 T), the exploration of novel contrast agents (CAs) for ultrahigh field MRI is urgently needed. Herein, we report polyethyleneimine (PEI)-coated TbF3 nanoparticles (NPs), which were synthesized by a facile solvothermal method, as potential dual-mode CAs for ultrahigh field MRI and X-ray computed tomography (CT). Owing to their strong paramagnetism, the TbF3 NPs showed excellent transverse relaxivity (395.77 mM-l.s-1) and negligible longitudinal relaxivity under an ultrahigh magnetic field (7 T) with a great potential as a T2-weighted MRI contrast agent. Furthermore, by comparison with the clinically used CT CAs (iohexol), the TbF3 NPs showed superior X-ray attenuation ability. The practical application for T2-weighted MRI and CT imaging was demonstrated with an animal model. Moreover, cell cytotoxicity and in vivo toxicity assessments implied the low toxicity of TbF3 NPs. In summary the above results indicate that TbF3 NPs are promising candidates for ultrahigh field MRI and CT dual-mode imaging.
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.