INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 12
·2988
·
IF 4.183
Xiuliang Zhu,Nan Lu,Ying Zhou,Shaoyan Xuan,Jiaojiao Zhang,Francesca Giampieri,Yongping Zhang,Fangfang Yang,Risheng Yu,Maurizio Battino,Zuhua Wang
Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.Keywords:pancreatic cancer;CKAAKN peptide;MRI contrast agent;polymer
研究领域:
肿瘤学
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医学影像学
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生物材料学
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DOI
PubMed
高影响因子
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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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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2014
·
IF 4.287
Xuehua Ma,An Gong,Bin Chen,Jianjun Zheng,Tianxiang Chen,Zheyu Shen,Aiguo Wu
Advances in contrast agents have greatly enhanced the sensitivity of magnetic resonance imaging (MRI) technique for early diagnosis of cancer. However, the commercial superparamagnetic iron oxide nanoparticles (SPION)-based contrast agents synthesized by co-precipitation method are not monodisperse with irregular morphologies and ununiform sizes. Other reported SPION-based contrast agents synthesized by solvothermal method or thermal decomposition method are limited by the bad water-dispersibility and low specificity to cancer cells. Herein, we propose a new strategy for exploring SPION-based MRI contrast agents with excellent water-dispersibility and high specificity to cancer cells. The SPION was synthesized by a polyol method and then entrapped into albumin nanospheres (AN). After that, a ligand folic acid (FA) was conjugated onto the surface of the AN to construct a SPION-AN-FA composite. The transmission electron microscope (TEM) and dynamic light scattering (DLS) results indicate that the SPION-AN-FA has a spherical shape, a uniform size and an excellent water-dispersibility (polydispersity index (PDI) <0.05). The results of laser scanning confocal microscope (LSCM) and flow cytometry demonstrate that the SPION-AN-FA nanoparticles are highly specific to MCF-7 and SPC-A-1 cells due to the recognition of ligand FA and folate receptor α (FRα). The r 2 / r 1 value of SPION-AN-FA is around 40, which is much higher than that of Resovist ® indicating that our SPION-AN-FA has a stronger T 2 shortening effect. The T 2 -weighted images of MCF-7 cells incubated with SPION-AN-FA are significantly darker than those of MCF-7 cells incubated with AN, indicating that our SPION-AN-FA has a strong MR imaging efficacy. In view of the excellent water-dispersibility, the high specificity to cancer cells and the strong MR imaging efficacy, our SPION-AN-FA can be used as a negative MR contrast agent.
研究领域:
医学影像
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纳米医学
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癌症研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Zhongtao Li,Jing Guo,Mengmeng Zhang,Guohua Li,Liguo Hao
Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd 2 O 3 ) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity ( r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd 2 O 3 to produce Gd 2 O 3 @MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity ( r 1 ) as high as 51.85 ± 1.38 mM −1 s −1 . Gd 2 O 3 @MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI.
研究领域:
材料科学
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纳米技术
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医学影像
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 40
·6413-6423
·
IF 4.776
Juanjuan Li,Ruitao Cha,Yulong Zhang,Hongbo Guo,Keying Long,Pangye Gao,Xiaohui Wang,Fengshan Zhou,Xingyu Jiang
Even though iron oxide (Fe3O4) nanoparticles are promising materials for magnetic resonance imaging (MRI) contrast agents, their biocompatibility and targeting efficacy still need to be improved. Herein, we modified glycyrrhetinic acid (GA) groups on Fe3O4 nanoparticles (Fe3O4@cGlu-GA) for liver tumor-targeted imaging. To evaluate the biocompatibility of these nanoparticles, we studied their cytotoxicity, hemolysis, and hepatotoxicity. We measured the uptake of Fe3O4@cGlu-GA nanoparticles in normal and liver tumor cells, then we investigated the specificity of Fe3O4@cGlu-GA nanoparticles in mouse models bearing subcutaneous and orthotopic liver tumors. With good biocompatibility and targeting efficacy both in vitro and in vivo, the Fe3O4@cGlu-GA nanoparticles are promising MRI contrast agents with ultralow hepatotoxicity and show great improvement on existing Fe3O4-based nanoparticles.
研究领域:
纳米技术
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医学成像
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药学
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
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2021
·Vol. 32
·期 11
·14932-14943
·
IF 2.478
Deng Huawei,Liu Jun,Zhang Hang,Li Chaorui,Liu Zhen,Chen Dihu
Multimodal imaging has attracted tremendous attention in biotechnology and nanomedicine applications. Monoclinic Gd 2 O 3 :Dy 3+ nanoparticles (NPs) with dual-color fluorescence imaging (FI) and magnetic resonance imaging (MRI) have been successfully synthesized by employing laser ablation in liquid (LAL) technique. The synthesized nanoparticles can be used as yellow fluorescence nanoprobe as well as blue ones due to their sharp and strong yellow and blue emissions. Magnetic resonance imaging (MRI) measurement shows that the longitudinal relaxivity (r 1 ) of the Gd 2 O 3 :1%Dy 3+ NPs is 4.5 times higher than that of the commercial Gd-DTPA. The experiment of in vitro cell fluorescence imaging and magnetic resonance imaging of female Balb/c mouse indicates that the Gd 2 O 3 :Dy 3+ NPs synthesized by LAL technique are promising candidates of dual-color FI nanoprobe and MRI contrast agent in further clinical applications.
研究领域:
生物技术
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纳米医学
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材料科学
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医学成像
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Zhiguo Qin,Bo Chen,Yu Mao,Chu Shi,Yan Li,Xiao Huang,Fang Yang,Ning Gu
Prussian blue nanoparticles (PBNPs), which belong to the iron-based metal–organic frameworks, are important biomedical agents. Reducing the size of PBNPs can bring improved functional properties, but unfortunately, has been a long-standing challenge. Herein, sub-5 nm ultrasmall PBNPs (USPBNPs) were successfully synthesized by using ethanol/water mixture as the solvent and polyvinyl pyrrolidone (PVP) as the surface capping agent. Adjusting the ethanol/water ratio is not only able to control the nucleation time and size of PBNPs but also tune the conformation of PVP molecules so as to prevent interparticle attachment and enlargement. At an ethanol/water ratio of 3:1, highly stable USPBNPs with a size of ∼3.4 nm were synthesized. Due to their large specific surface area, they demonstrated high peroxidase-like and catalase-like activities, which outperform PBNPs synthesized by a conventional method. In addition, they also showed a high longitudinal relaxation rate (r1) of 1.3 mM–1 S–1, suggesting their potential to be used as T1 MRI agent.
研究领域:
生物医学工程
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纳米医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 32
·22335-22345
·
IF 3.9
Ziwei Duan,Changjiang Liu,Junjie Tang,Ruling Zhang,Danfeng Peng,Ruitao Lu,Zong Cao,Dalin Wu
Medical imaging contrast agents that are able to provide detailed biological information have attracted increasing attention. Among the new emerging imaging contrast agents, 19F magnetic resonance imaging contrast agents (19F MRI CAs) are extremely promising for their weak background disturbing signal from the body. However, to prepare 19F MRI CAs with a long T2 relaxation time and excellent biocompatibility in a simple and highly effective strategy is still a challenge. Herein, we report a new type of 19F MRI hydrogel nanocontrast agents (19F MRI HNCAs) synthesized by a surfactant-free emulsion polymerization with commercial fluorinated monomers. The T2 relaxation time of 19F MRI HNCA-1 was found to be 25–40 ms, guaranteeing its good imaging ability in vitro. In addition, according to an investigation into the relationship between the fluorine content and 19F MRI signal intensity, the 19F MRI signal intensity was not only determined by the fluorine content in 19F MRI HNCAs but also by the hydration microenvironment around the fluorine atoms. Moreover, 19F MRI HNCAs demonstrated excellent biocompatibility and imaging capability inside cells. The primary exploration demonstrated that 19F MRI HNCAs as a new type of 19F MRI contrast agent hold potential for imaging lesion sites and tracking cells in vivo by 19F MRI technology.
研究领域:
医学成像
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材料科学
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纳米技术
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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
JOURNAL OF RARE EARTHS
·
2021
·
IF 3.712
Jia Zhang,Zhiyan Lin,Minzhi Zhao,Weibing Xu,Fang Nian
Gadolinium (III)-based T 1 contrast agents have been widely used in clinical MRI. In this study, salicylic acid-gadolinium chelate was prepared via directly coordination reaction of gadolinium ion and salicylic acid. Then, three polyethylene glycols with different molecular weight were modified on the surface of salicylic acid-gadolinium by simple chemical coupling to construct three core-shell structural Gd based composites. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization results show that the composite is a spherical particle with a diameter of about 100–200 nm. The longitudinal relaxation rate r 1 of the Gal-PEG-2000 is 11.097 (mmol/L) −1 /s, and the ratio of r 2 / r 1 is as low as 2.53. The composite shows good liver and intestines MRI performances after being used in in vivo imaging, showing a good prospect of biological application.
研究领域:
医学成像
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纳米技术
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2019
·Vol. 83
·期 4
·622-632
·
IF 1.297
Song Xiaowei,Yan Guanghai,Quan Songshi,Jin Enhao,Quan Jishan,Jin Guangyu
To noninvasively monitor the effect of gene therapy and achieve an optimal therapeutic effect, liposomes encapsulated polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles (SPION) with dual functions of MRI diagnosis and gene therapy were prepared. SPION was synthesized via co-precipitation, and then modified with PEI via thiourea reaction. The liposomes encapsulating PEI-SPION (LP-PEI-SPION) were prepared by ethanol injection. Fourier transform infrared spectra confirmed that PEI was successfully modified onto SPION, and thermogravimetric analysis indicated that the PEI content was about 17.1%. The LP-PEI-SPION/DNA had a small particle size of 253.07 ± 0.90 nm. LP-PEI-SPION/DNA had low cytotoxicity with more than 80% of the cell survival rates and high transfection efficiency compared with Lipofectamine® 2000/DNA. Additionally, it also showed good MRI effect on three cell lines. The liposomes encapsulating PEI-SPION (lipopolyplexes) have been successfully prepared as MRI contrast agents and gene delivery vectors, which may have great theoretical research significance and clinical potentials.Abbreviations: PEI, polyethylenimine; SPION, superparamagnetic iron oxide nanoparticles; LP-PEI-SPION, liposomes encapsulating PEI-SPION; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; ICP-MS, inductively coupled plasma mass spectrometry; XRD, X-ray diffraction; TEM, transmission electron microscope; TGA, thermogravimetric analysis; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; Chol, cholesterol.
研究领域:
生物医学工程
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纳米技术
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基因治疗
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分子生物学
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医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 11
·2470-2478
·
IF 3.641
Tu Rong,You Xiaoguang,Ding Zhichao,Wu Huanyu,Zhao Linlu,Qiu Zhi,Wei Junjie,Yang Xiaofeng
Development of imaging methods that can detect target molecules will be of great significance for non-invasive molecular diagnosis. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a broadly expressed target, and VEGFR-2-specific agents have been used in biological therapy.
In this study, amine-reactive coupling was used to label the polypeptide VEGF125–136 with a Gd(DOTA) complex to create a magnetic resonance contrast agent, VEGF125–136-Gd, which binds to VEGFR-2. Using T1-weighted magnetic resonance imaging, we explored the tumor cell-targeting
ability of VEGF125–136-Gd and its enhancement of T1-weighted image intensity using human hepatoma (HepG2) cells and found that the signal-to-noise ratio (SNR) increased commensurately with the concentration of VEGF125–136-Gd. At a concentration of 2 mM, the SNR produced by VEGF125–136-Gd
was 5.4-fold higher than that produced by a Gd-labelled non-targeting polypeptide (NTPP-Gd) control. We also evaluated the tumor-targeting efficiency of VEGF125–136-Gd in nude mice injected with human hepatoma (HepG2) cells. Preliminary in vivo imaging of VEGFR-2 in tumor tissue
revealed a targeting peak 60 min post administration of VEGF125–136-Gd, the intensity of which was 23% higher than the SNR of NTPP-Gd at the same time point. Our findings may help lay the foundation for clinical applications of VEGF125–136-Gd in targeted imaging.
研究领域:
医学影像
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癌症生物学
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分子生物学
·
药学
✓ 已验证
DOI
高影响因子
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