JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yinghui Ding,Xinzhong Ruan,Kun Shu,Weiyuan Xu,Yao Liu,Gengshen Mo,Jiao Xu,Yong Jian,Jilai Zhang,Lingfeng Zhang,Keren Wang,Ji-Ting Hou,Jianliang Shen,Zhihan Yan,Fangfu Ye,Jiang Zhu,Lixiong Dai
Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the “peroxidase cycle” as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.
研究领域:
医学成像
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药物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2023
·Vol. 332
·期 4
·1237-1244
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IF 1.6
Xi Wenke,Zhang Ge,Xue Jingquan,Li Juan,Liu Yu,Wang Jianjun,Yang Wenjiang
Multimodal imaging has become a trend in the development of molecular imaging. For SPECT/MRI dual-modality imaging, we developed a SPECT/MRI dual-modality probe based on superparamagnetic iron oxide nanoparticles. RGDyk peptide and DTPA chelator were used to realize the functionalization of nanoparticles. Both SPECT imaging and T2-weighted MR imaging in vivo on 4T1 tumor-bearing mice showed targeting of the probe, demonstrating the potential of the SPECT/MRI dual-modality probe as a tool for tumor evaluation and diagnosis.
研究领域:
医学影像学
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分子生物学
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纳米医学
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DOI
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Jialei Han,Ziwei Duan,Changjiang Liu,Yadong Liu,Xinyu Zhao,Bo Wang,Shuaishuai Cao,Dalin Wu
19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin–spin) relaxation time (T2), short longitudinal (or spin–lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on β-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.
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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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 21
·4752-4762
·
IF 7
Zhe Yang,Yueqi Zhao,Yang Li,Lei Song,Yangliu Lin,Kaimeng Liu,Yujia Zhang,Andrei V. Zvyagin,Linan Fang,Yuanqing Sun,Bai Yang,Quan Lin
Surgical resection is the main method for oral tongue squamous cell carcinoma (OTSCC) treatment. However, the oral physiological function and aesthetics may be seriously damaged during the operation with a high risk of recurrence. Therefore, it is important to develop an alternative strategy with precise guidance for OTSCC treatment. Herein, multifunctional Au/Mn nanodots (NDs) are designed and synthesized. They can perform multimodal bioimaging, including computed tomography (CT) and magnetic resonance imaging (MRI) simultaneously, and exhibit bright near-infrared fluorescence imaging (FI) for navigation, and even integrate photothermal therapy (PTT) property. The localization of OTSCC relies on visual and tactile cues of surgeons while lacking noninvasive pretreament labeling and guidance. Au/Mn NDs provide CT/MRI imaging, giving two means of accurate positioning pretherapy. Meanwhile, the fluorescence of the Au/Mn NDs in the near-infrared region (NIR) is beneficial for noninvasive labeling and intuitive observation with the naked eye to determine the tumor boundary during PTT. Further, Au/Mn NDs showed excellent results in ablating tumors in vivo. Above all, the Au/Mn NDs provide a key platform for multimodal bioimaging and PTT in a single nanoagent, which demonstrated attractive performance for OTSCC treatment.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 43
·9055-9066
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IF 6.331
Lili Hao,Peng Wang,Zhenxu Wu,Zongliang Wang,Yu Wang,Yongzhan Zhu,Zhiqiang Xu,Min Guo,Jiansong Ji,Peibiao Zhang
Single-modal magnetic resonance imaging (MRI) contrast agents sometimes cause signal confusion in clinical diagnosis. Utilizing ligands to endow iron oxide nanoparticles (IO NPs) with excellent dual-modal MRI contrast efficiency might be an effective strategy to improve diagnostic accuracy. This work presents the development of a special ligand-assisted one-pot approach for the preparation of super-hydrophilic magnetic NPs with excellent water dispersion, biocompatibility and T1–T2 dual-modal contrast enhancement properties. In addition, the strong binding capacity between the ethylenediamine tetramethylenephosphonic acid (EDTMP) ligand and water molecules induced by the presence of abundant hydrogen bonds significantly improves spin–lattice (T1) and spin–spin (T2) imaging of the IO core. After being modified with the EDTMP ligand, the T2 relaxation rate of the IO core is dramatically increased from 71.78 mM−1 s−1 to 452.38 mM−1 s−1, and a moderate T1 relaxation rate (11.61 mM−1 s−1) is observed simultaneously, implying that the NPs with an average size of 9.7 nm may be potential candidates as high-efficiency T1–T2 MRI contrast agents. This fundamental technique of using super-hydrophilicity ligands to endow IO NPs with dual-modal contrast properties without size change and damage in the T2 contrast effect may provide a useful strategy to facilitate the application of magnetic NPs in the field of medical diagnosis.
研究领域:
材料科学
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纳米技术
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医学成像
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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
INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Yong Jian,Gengshen Mo,Weiyuan Xu,Yao Liu,Zhichao Zhang,Yinghui Ding,Ruonan Gao,Jiao Xu,Jiang Zhu,Kun Shu,Zhihan Yan,Fabio Carniato,Carlos Platas-Iglesias,Fangfu Ye,Mauro Botta,Lixiong Dai
In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.
研究领域:
化学
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材料科学
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医学成像
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药理学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Mengyang Zhou,Yifei Wang,Yaning Xia,Yinhua Li,Jianfeng Bao,Yong Zhang,Jingliang Cheng,Yupeng Shi
Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy) 3 Cl 2 and GdCl 3 , which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd 3+ , and the singlet oxygen generation of Ru(dcbpy) 3 Cl 2 , are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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分子成像
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 10
·2051
·
IF 6.525
Wei Zhou,Jiandong Huang,Qingwei Xiao,Shunmin Hu,Shijia Li,Jie Zheng,Zhiyun Du,Jiangling Peng,Huixiong Chen
The prostate specific membrane antigen (PSMA), extensively overexpressed on prostate cancer (PCa) cell surface, has been validated as a diagnostic biomarker for PCa. However, insufficient attention has been paid to the development of PSMA-specific probes loaded with small chemical molecules for the in vivo molecular imaging of PCa. In this study, we innovatively labelled superparamagnetic iron oxide nanoparticles with a PSMA-targeting Glu-Urea-Lys scaffold. An optimized synthetic route was developed to offer a physiochemically stable probe. The probe demonstrated high binding affinity (0.38 ± 0.08 μg(Fe)/mL) and binding specificity to PSMA expressed on prostate cancer cell surface in vitro. In a xenograft PCa mouse model, significant negative contrast of the implanted prostate cancer xenograft could be specifically observed by MRI 6 h after tail vein injection of the tracer (Fe, 20 mg/kg), exhibiting its potential to exclusively enhance magnetic resonance detection of PCa.Keywords:prostate cancer;PSMA;molecular imaging;MRI contrast agent;SPIONs
研究领域:
肿瘤学
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医学成像
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Sa Huang,Peng Chen,Chen Xu
Nowadays, cancer has become a serious threat to public health worldwide. Early and precise diagnosis is critical for the detection, monitoring and management of cancer. Herein, a facile strategy for developing a fluorescence/MRI dual-modal nanoprobe (FA-PEI-NaGdF 4 :Eu nanoparticles) has been reported for targeted cancer cell imaging. The fluorescence/MRI nanoprobes have strong fluorescence and the high signal-to-noise ratio, which is suitable for the fluorescence imaging. Moreover, the FA-PEI-NaGdF 4 :Eu nanoprobes have high longitudinal relaxivity, making them suitable for T 1 -weighted MR imaging. Additionally, due to modification with FA , the fluorescence/MRI nanoprobes could target cancer cells that possessed large numbers of folate receptors. The results of the cytotoxicity assay revealed that the nanoprobes had the excellent biocompatibility. With the high biocompatibility, excellent imaging performance and superior targeting, the FA-PEI-NaGdF 4 :Eu nanoprobes can be used as a promising candidate for targeted fluorescence/MRI cancer cell imaging and would bring more opportunities for the biomedical applications.
研究领域:
医学影像学
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生物材料学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 27
·22575-22585
·
IF 3.289
Yuan-Peng Rui,Bo Liang,Fenglin Hu,Jie Xu,Yi-Feng Peng,Pei-Hao Yin,Yourong Duan,Chunfu Zhang,Hongchen Gu
Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with high stability in physiological conditions have great potential for T1-weighted MRI. In the current study, we developed a procedure for ultra-large-scale production of USPIOs (1.5 kg per batch) for T1-weighted MRI. The USPIOs were coated with poly(acrylic acid) (PAA@USPIOs). They were uniform in size (∼4.5 nm) and very stable in physiological conditions even after being sterilized in an autoclave. Due to their small size, the PAA@USPIOs demonstrated good T1 MRI contrast effect and could be used for both first-pass and steady-state magnetic resonance angiography (MRA). After being injected with PAA@USPIOs at the dose of 135 μmol Fe per kg, the head–neck vasculatures and abdominal artery of rabbits and the coronary artery of pigs could be clearly visualized by T1-weighted MRI. Moreover, PAA@USPIOs were highly tolerable by animals. Our study indicated that the procedure developed in this study has great promise for large-scale production of USPIOs for T1-weighted MRI for future clinical applications.
研究领域:
医学影像学
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纳米医学
·
生物材料
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产品关联
DOI
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-8
·
IF 4.6
Xin Jia-Xiang,Yang Guang,Zhang Huojun,Li Jianqi,Fu Caixia,Wang Jiachen,Tong Rui,Ren Yan,Wei Da-Xiu,Yao Ye-Feng
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have made great successes in clinical diagnosis, medical research, and neurological science. MRI provides high resolution anatomical images of tissues/organs, and MRS provides information of the functional molecules related to a specific tissue/organ. However, it is difficult for classic MRI/MRS to selectively image/probe a specific metabolite molecule other than the water or fat in tissues/organs. This greatly limits their applications on the study of the molecular mechanism(s) of metabolism and disease. Herein, we report a series of molecularly targeted MRI/MRS methods to target specific molecules. The optimal control method was used to efficiently prepare the singlet spin orders of varied multi-spin systems and in turn greatly expand the choice of the targeted molecules in the molecularly targeted MRI/MRS. Several molecules, such as N -acetyl- l -aspartic acid (NAA), dopamine (DA), and a tripeptide (alanine-glycine-glycine, AGG), have been used as targeted molecules for molecularly targeted MRI and MRS. We show in vivo NAA-targeted 1 H MRS spectrum of a human brain. The high-resolution signal of NAA suggests a promising way to study important issues in molecular biology at the molecular level, e.g., measuring the local pH value of tissue in vivo, demonstrating the high potential of such methods in medicine.
研究领域:
医学影像学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 22
·4261-4273
·
IF 7.571
Hui Guo,Fangzhe Liu,Enqi Liu,Shanshan Wei,Wenbo Sun,Baoqiang Liu,Guoying Sun,Lehui Lu
Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA–Cys–PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA–Cys–PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM−1 s−1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.
研究领域:
纳米技术
·
癌症治疗
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磁共振成像（MRI）
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药物递送系统
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光动力疗法
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）