JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 7.3
Weiyuan Xu,Xinjian Ye,Min Wu,Xin Jiang,Lik Hang Hugo TSE,Yanjuan Gu,Kun Shu,Liuhui Xu,Yong Jian,Gengshen Mo,Jiao Xu,Yinghui Ding,Ruonan Gao,Jianliang Shen,Fangfu Ye,Zhihan Yan,Lixiong Dai
The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.
研究领域:
医学影像学
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分子生物学
·
化学
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DOI
PubMed
高影响因子
Small
·
2015
·Vol. 11
·期 42
·5675-5686
·
IF 8.368
Qiao An,Jing Liu,Meng Yu,Jiaxun Wan,Dian Li,Changchun Wang,Chunying Chen,Jia Guo
To overcome traditional barriers in optical imaging and microscopy, optoacoustic-imaging has been changed to combine the accuracy of spectroscopy with the depth resolution of ultrasound, achieving a novel modality with powerful in vivo imaging. However, magnetic resonance imaging provides better spatial and anatomical resolution. Thus, a single hybrid nanoprobe that allows for simultaneous multimodal imaging is significant not only for cutting edge research in imaging science, but also for accurate clinical diagnosis. A core-shell-structured coordination polymer composite microsphere has been designed for in vivo multimodality imaging. It consists of a Fe 3 O 4 nanocluster core, a carbon sandwiched layer, and a carbocyanine-Gd III (Cy-Gd III ) coordination polymer outer shell (Fe 3 O 4 @C@Cy-Gd III ). Folic acid-conjugated poly(ethylene glycol) chains are embedded within the coordination polymer shell to achieve extended circulation and targeted delivery of probe particles in vivo. Control of Fe 3 O 4 core grain sizes results in optimal r 2 relaxivity (224.5 × 10 –3 m −1 s -1 ) for T 2 -weighted magnetic resonance imaging. Cy-Gd III coordination polymers are also regulated to obtain a maximum 25.1% of Cy ligands and 5.2% of Gd III ions for near-infrared fluorescence and T 1 -weighted magnetic resonance imaging, respectively. The results demonstrate their impressive abilities for targeted, multimodal, and reliable imaging.
研究领域:
医学影像学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Chenchen Liu,Xiaoming Liu,Zhihao Wei,Zong Chang,Yaowei Bai,Pei Zeng,Qi Cao,Changjun Tie,Ziqiao Lei,Peng Sun,Huageng Liang,Qinchao Sun,Xiaoping Zhang
Magnetic resonance angiography (MRA) contrast agents are extensively utilized in clinical practice due to their capability of improving the image resolution and sensitivity. However, the clinically approved MRA contrast agents have the disadvantages of a limited acquisition time window and high dose administration for effective imaging. Herein, albumin-coated gadolinium-based nanoparticles (BSA-Gd) were meticulously developed for in vivo ultrahigh-resolution MRA. Compared to Gd-DTPA, BSA-Gd exhibits a significantly higher longitudinal relaxivity (r1 = 76.7 mM–1 s–1), nearly 16-fold greater than that of Gd-DTPA, and an extended blood circulation time (t1/2 = 40 min), enabling a dramatically enhanced high-resolution imaging of microvessels (sub-200 μm) and low dose imaging (about 1/16 that of Gd-DTPA). Furthermore, the clinically significant fine vessels were successfully mapped in large mammals, including a circle of Willis, kidney and liver vascular branches, tumor vessels, and differentiated arteries from veins using dynamic contrast-enhanced MRA BSA-Gd, and have superior imaging capability and biocompatibility, and their clinical applications hold substantial promise.
研究领域:
医学影像学
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纳米医学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Ting Zhou,Yanzhi Dong,Xiaoyi Wang,Ruxia Liu,Ran Cheng,Jinbin Pan,Xuejun Zhang,Shao-Kai Sun
Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T 1 relaxivity (12.52 m m −1 s −1 ), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.
研究领域:
医学影像学
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生物材料学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2015
·
IF 8.557
Ling'e Zhang,Leyong Zeng,Yuanwei Pan,Song Luo,Wenzhi Ren,An Gong,Xuehua Ma,Hongze Liang,Guangming Lu,Aiguo Wu
Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL) nanocomposites have potential application for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT) of cancers using the light stability and biocompatibility of TiO 2 inorganic photosensitizer. However, TiO 2 inorganic photosensitizer could only be excited by ultraviolet (UV) light, which was harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted NaGdF 4 :Yb/Tm@SiO 2 @TiO 2 nanocomposites (FA-Gd-Si-Ti NPs) were constructed and synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic PDT, in which TiO 2 component could be excited by NIR light due to the UCL performance of NaGdF 4 :Yb/Tm component converting NIR to UV light. The results showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T 1 -weighted MRI contrast agents with high longitudinal relaxivity (r 1 ) of 4.53 m m −1 s −1 , also in vivo MRI of nude mice showed “bright” signal in MCF-7 tumor. Under the irradiation of 980 nm laser at the power density of 0.6 W/cm 2 for 20 min, the viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice model showed that the inhibition ratio of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with that of nude mice in control group. Based on the deep penetration of NIR light and the good biocompatibility of TiO 2 inorganic photosensitizer, the as-prepared FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive PDT of cancers in deep tissues.
研究领域:
生物医学工程
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肿瘤学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2020
·Vol. 37
·期 4
·2000044
·
IF 3.099
Kehan Xu,Na Xu,Yanchao Zhu,Mengsi Zhang,Weijun Tang,Yun Ding,Aiguo Hu
Conformity of two biological imaging entities, magnetic resonance imaging (MRI) and fluorescence imaging, is achieved through co-assembly of a Gd(III)-based metallosurfactant, conjugated polymeric nanoparticles, and amphiphilic block copolymer F127 (PEO 106 PPO 70 PEO 106 ) followed by crosslinking with organosilica. The cross-linked micelles with a size around 100 nm exhibit outstanding dispersion stability in aqueous and phosphate buffered saline solutions, bright fluorescence emission, and high relaxivities, providing a new approach to synthesize highly efficient bimodal contrast agents. The relaxivities of the co-assembled micelles are synergistically enhanced by incorporation of Gd(III) complexes with high hydration number ( q = 3) and elongation of rotation correlation time to achieve r 1 values up to 105.37 m m −1 s −1 (at 1.5 T), which is over 20 times that of clinically used MRI contrast agents and among the highest values of all the nanoparticular MRI contrast agents. The external PEO layer endows these micelles with very low cytotoxicity for both in vitro and in vivo imaging. Meanwhile, thanks to the enhanced permeability and retention effect originating from their nanoscale sizes, the bimodal contrast agents show a prolonged blood circulation time in vivo and targeted accumulation at tumor regions to display outstanding MRI imaging performance.
研究领域:
生物医学工程
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材料科学
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影像医学
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产品关联
DOI
高影响因子
Nano Research
·
2017
·Vol. 11
·期 2
·929-939
·
IF 7.354
He Zhimei,Zhang Penghui,Xiao Yan,Li Jingjing,Yang Fang,Liu Yang,Zhang Jian-Rong,Zhu Jun-Jie
During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T 1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and “turned on” T 1 signals in vitro , showing great promise for diagnosis and treatment.
研究领域:
癌症治疗
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纳米技术
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药物递送系统
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磁共振成像
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生物医学工程
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Yuping Zhang,Ke Xiang,Jinbin Pan,Ran Cheng,Shao-Kai Sun
Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM–1 s–1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.
研究领域:
医学影像
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肾脏生理
·
药物化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Dinghu Weng,Rong Guo,Changling Dong,Yuan Luo,Dasheng Qiu,Liying Xu,Guobin Xu
The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM–1 s–1 and 5.323 mM–1 s–1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.
研究领域:
医学成像
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肿瘤学
·
药物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2019
·
IF 13.903
Qinjie Weng,Xi Hu,Jiahuan Zheng,Fan Xia,Nan Wang,Hongwei Liao,Ying Liu,Dokyoon Kim,Jianan Liu,Fangyuan Li,Qiaojun He,Bo Yang,Chunying Chen,Taeghwan Hyeon,Daishun Ling
Gadolinium-based contrast agents (GBCAs) are widely used for T1-weighted magnetic resonance imaging (MRI) in clinic diagnosis. However, a major drawback of GBCAs is that they can increase the toxicological risk of nephrogenic systemic fibrosis (NSF) in patients with advanced renal dysfunction. Hence, safer alternatives to GBCAs are currently in demand, especially for patients with renal diseases. Here we investigated the potential of polyethylene glycol (PEG)-stabilized iron oxide nanoclusters (IONCs) as biocompatible T1MRI contrast agents and systematically evaluated their NSF-related risk in rats with renal failure. We profiled the distribution, excretion, histopathological alterations, and fibrotic gene expressions after administration of IONCs and GBCAs. Our results showed that, compared with GBCAs, IONCs exhibited dramatically improved biosafety and a much lower risk of causing NSF, suggesting the feasibility of substituting GBCAs with IONCs in clinical MRI diagnosis of patients with renal diseases.
研究领域:
医学影像
·
纳米技术
·
药理学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2015
·Vol. 39
·期 5
·4020-4025
·
IF 3.086
Di Wu,Lingling Song,Zhenping Qi,Dapeng Qu
Multi-modal imaging in tissue and animals has integrated the advantages of individual molecular imaging modalities and shown great potential in both pre-clinical and clinical fields. In the present work, a high-performance nanoparticulate contrast agent based on PEGylated gadolinium hydroxycarbonate nanoparticles (PEG-GdNPs) was designed and synthesized via a facile approach. Due to the outstanding X-ray absorption coefficient/K-edge value and the presence of unpaired 4f electrons of element Gd, our well-prepared nanoprobes were successfully used as dual-modal contrast agents for in vivo synergistic magnetic resonance and X-ray computed tomography imaging. Bio-distribution of the nanoparticles was further studied via in vivo long-term tracking during the imaging process, revealing that most of the nanoprobes could accumulate in the liver and therefore act as a liver-targeted imaging agent. Moreover, toxicity including cell viability, blood biochemical assay, as well as changes in body weight and histology indicated the low systemic toxicity of our nanoprobes. Taken together, we believe that PEG-GdNPs with their excellent imaging capability and high biocompatibility may find widespread application in the field of biomedicine.
研究领域:
医学影像
·
纳米技术
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）