Analytical Methods
·
2017
·Vol. 9
·期 21
·3099-3104
·
IF 1.9
Dong Li,Minghui Hua,Kun Fang,Rong Liang
High-performance magnetic resonance (MR) imaging contrast agents are the key to reliable and accurate diagnosis of diseases using the MR imaging technique. In particular, dual-modal MR imaging nanoprobes that integrated the advantages of a high contrast effect and impressive sensitivity of T1- and T2-weighted MR imaging, respectively, have attracted increasing attention in recent years. However, the current methods for the fabrication of the dual-modal MR imaging nanoprobes suffer from a tedious synthesis procedure, harsh synthesis condition and ambiguous toxicity, strongly hindering their clinic transformation. Herein, we proposed a biomineralization approach for the fabrication of bovine serum albumin (BSA)–Fe3O4 nanoparticles with undoubted biosafety and robust T1 and T2 MR imaging ability in a facile way under mild conditions. BSA not only served as a template to control the growth of nanocrystal, but also enabled the favorable water solubility of the nanoprobe. The outstanding biocompatibility of BSA–Fe3O4 nanoparticles was proven by systematic in vitro and in vivo toxicity assessments, and dual-modal T1 and T2 MR imaging in vivo was achieved successfully. In addition, the nanoprobe was successfully applied for in vivo MR imaging of liver with a broad time window, and the metabolic investigation of BSA–Fe3O4 nanoparticles revealed that they could be eliminated from the body, ensuring a negligible adverse effect. The proposed biomineralization approach opens a new way for the fabrication of dual-modal MR contrast imaging nanoprobe with undoubted biosafety, and other functional proteins also exhibit great potential for the fabrication of dual-modal MR contrast imaging nanoprobe with specific functions with respect to biomineralization.
研究领域:
医学影像学
·
材料科学
·
生物医学工程
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DOI
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Zhongzhong Lu,Jincong Yan,Mingsheng Xu,Lina Sun,Jihuan Liu,Ye Zhang,Lei Shi,Xifeng Fei,Yi Cao,Renjun Pei
Magnetic resonance imaging (MRI), one of the most general imaging techniques in the clinic, is widely employed for tumor diagnosis with the assistance of contrast agents (CAs). However, currently available CAs in the clinic suffer from shortcomings of a short blood circulation time, lack of specificity to pathological location, insufficient imaging window, and potential biotoxicity of the gadolinium ion. To overcome these problems, on the basis of extremely small iron oxide nanoparticles (ESIONPs), a hypoxia-responsive T1-to-T2 switchable MRI contrast agent was designed and constructed. In detail, polyacrylic acid-modified ESIONPs (ESIONPs-PAA) were first synthesized, and then, nitroimidazole derivatives and cysteine molecules were sequentially coupled on the surface of ESIONPs-PAA to obtain a hypoxia-responsive MRI contrast agent (HR-ESIONPs). Since 2-nitroimidazole and cysteine molecules on the surface of HR-ESIONPs can form an irreversible bond induced by the nitroreductase in the hypoxic tumor microenvironment, monodispersed HR-ESIONPs could transform into the nanocluster form, which can specially provide T2 contrast enhancement. In vitro experiments show that monodispersed HR-ESIONPs could effectively aggregate in the mimical hypoxic environment of tumors and switch from a T1 to T2 contrast agent. Moreover, in vivo experiments further confirm that HR-ESIONPs could effectively accumulate and realize the MRI signal switch from T1 to T2 contrast enhancement in tumors originating from the aggregation of HR-ESIONPs induced by the hypoxic environment, which promotes the diagnostic precision of tumors. Additionally, with the confirmation of favorable biosafety on cells and mice, hypoxia-responsive HR-ESIONPs are potential platforms to improve the diagnostic accuracy and sensitivity of MRI for tumors.
研究领域:
医学影像学
·
纳米医学
·
肿瘤学
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产品关联
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 28
·13632-13646
·
IF 4.682
Zhu Wenhao,Wu Zhenxu,Wang Peng,Liu Tianyi,Guo Min,Ji Jiansong,He Mingfeng,Wang Haifeng,Zhang Peibiao
Within brain tissue engineering, stem cell implantation assisted by biodegradable injectable scaffolds is a crucial method. However, implanted scaffolds, especially microcarriers, may translocate due to the fluidity of the materials. Therefore, the development of an MRI contrast enhancement microcarrier, which could noninvasively trace the location of the implant in vivo, is necessary to guide the evaluation of treatment prognosis. In this study, GdPO 4 ·H 2 O nanoparticles were utilized as the dispersed phase to endow PLGA microcarriers with T1-weighted MRI contrast ability. By adjusting the dispersed phase of Gd compound nanoparticle in PLGA Matrix, a cross-comparison experiment between MRI contrast enhancement imaging and biocompatibility was conducted, and 0.8% Gd was found to be the most suitable rate for preparing nano-composites. Moreover, 0.8% Gd/PLGA microcarriers were suspension-cultured with stem cells in vitro and implanted into traumatic brain injury rats in vivo. Excellent cytocompatibility and enhancement of the T1 phase of MRI were confirmed. This work created a T1-weighted MRI contrast-enhanced microcarrier, which provides a clinical noninvasive tracing cell scaffold for brain tissue engineering.
研究领域:
生物医学工程
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干细胞研究
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医学影像
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神经科学
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产品关联
DOI
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Jiali Li,Xue Jiang,Lihuan Shang,Zhen Li,Conglian Yang,Yan Luo,Daoyu Hu,Yaqi Shen,Zhiping Zhang
This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn2+ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM−1·s−1. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.
研究领域:
医学影像学
·
纳米医学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2021
·Vol. 11
·期 10
·2601
·
IF 5.076
Xiangyan Wang,Lei Chen,Jianxian Ge,Mohammad Javad Afshari,Lei Yang,Qingqing Miao,Ruixue Duan,Jiabin Cui,Chunyi Liu,Jianfeng Zeng,Jian Zhong,Mingyuan Gao
Precise diagnosis and monitoring of cancer depend on the development of advanced technologies for in vivo imaging. Owing to the merits of outstanding spatial resolution and excellent soft-tissue contrast, the application of magnetic resonance imaging (MRI) in biomedicine is of great importance. Herein, Angiopep-2 (ANG), which can simultaneously help to cross the blood-brain barrier and target the glioblastoma cells, was rationally combined with the 3.3 nm-sized ultra-small iron oxide (Fe3O4) to construct high-performance MRI nanoprobes (Fe3O4-ANG NPs) for glioblastoma diagnosis. The in vitro experiments show that the resultant Fe3O4-ANG NPs not only exhibit favorable relaxation properties and colloidal stability, but also have low toxicity and high specificity to glioblastoma cells, which provide critical prerequisites for the in vivo tumor imaging. Furthermore, in vivo imaging results show that the Fe3O4-ANG NPs exhibit good targeting ability toward subcutaneous and orthotopic glioblastoma model, manifesting an obvious contrast enhancement effect on theT1-weighted MR image, which demonstrates promising potential in clinical application.Keywords:ultra-small iron oxide nanoparticles;glioblastoma;MRI;T1contrast agent
研究领域:
生物医学工程
·
癌症诊断
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纳米技术
·
磁共振成像
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DOI
PubMed
高影响因子
Materialia
·
2022
·
IF 0
Jianfeng Yang,Qingling Zhao,Zehao Zang,Shuquan Zhang,Ziwu Wang,Lanlan Li,Xiaofei Yu,Xiaojing Yang,Zunming Lu,Xinghua Zhang
Magnetic resonance imaging (MRI) contrast agents with high relaxivity is of great importance for clinical diagnosis. Here we propose an effective method to enhance the relaxivity of MRI contrast agents. Ultra-small gadolinium oxide nanoparticles (Gd 2 O 3 NPs) with different surface ligands were prepared by coprecipitation method, and the polyacrylic acid (PAA) modulated Gd 2 O 3 NPs (PAA-Gd 2 O 3 ) have the high r 1 relaxivity of 53.34 mM –1 s –1 , which is mainly induced by the strong affinity between PAA and water molecules. In addition, PAA modulated Gd 2 O 3 NPs were successfully loaded on Au@MSNs (Au nanorod coated with mesoporous silica , Gd 2 O 3 /Au@MSNs) with enhanced affinity between Gd 3+ and water molecules, as well as increased motional time of Gd 3+ . Therefore, the r 1 relaxivity of Gd 2 O 3 /Au@MSNs can be up to 64.53 mM –1 s –1 , which is 17 times of the commercial agent Gd-DTPA. The Gd 2 O 3 /Au@MSNs NPs also have a low r 2 /r 1 of 1.04 and good computed tomography (CT) imaging performance, as well as good biocomatibility, which have great potential applications in multimodal bioimaging.
研究领域:
医学影像学
·
纳米医学
·
生物材料学
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DOI
BIOCONJUGATE CHEMISTRY
·
2023
·
IF 4.7
Zhongzhong Lu,Jincong Yan,Guangyue Zu,Mingsheng Xu,Jihuan Liu,Ye Zhang,Lei Shi,Xifeng Fei,Yi Cao,Renjun Pei
To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T1 and T2 contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T2-to-T1-switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4′-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T2-to-T1-switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the r2/r1 ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T2 to T1 contrast enhancement. This T2-to-T1-switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.
研究领域:
医学影像学
·
纳米医学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 43
·9055-9066
·
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
·
纳米技术
·
医学成像
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2026
·
IF 17.3
Zhang Huan,Liu Minrui,Zhou Zhongqin,Ye Pengfei,Wen Lingyi,Feng Quanqing,Song Ningning,Wang Yanyun,Ma Guohang,Sun Ran,Zhang Kun,Wu Qihong,Zhang Meng,Wang Yining,Guo Yingkun,Fan Haiming
Accurate
magnetic resonance imaging (MRI) of microvascular
occlusive
diseases, exemplified by subsegmental pulmonary embolism (SSPE), remains
a clinical challenge because of the intrinsic limitations of clinically
available Gd-based small molecular contrast agents (CAs). Ultrasmall
iron oxide nanoparticles (USIOs)-based CAs have emerged as promising
alternatives, offering adjustable MRI T 1 relaxivity, favorable pharmacokinetics, and high biocompatibility;
however, their performance is critically hampered by inefficient atomic
utilization for MR T 1 relaxivity enhancement.
Herein, we report Mg-doped USIOs MRI CAs with high atomic utilization
efficiency, where incorporating a biocompatible Mg dopant into surface
octahedral-site Fe vacancies substantially boosts the T 1 relaxivity, enabling accurate detection of SSPE-associated
structural and perfusion abnormalities. The Mg 0.03 -USIOs
exhibit a 261-fold enhancement of T 1 relaxivity
contribution by the Mg dopant, achieving an exceptionally high T 1 relaxivity of 12.6 mM −1 s −1 . Such a high atomic utilization efficiency could
stem from the promoted spin polarization and ferromagnetic spin alignment
through the surface Mg doping, which considerably boosts the magnetic
moment and outer-sphere relaxation contribution. Further in vivo MRI studies in a pig SSPE model demonstrated that the
Mg 0.03 -USIOs enabled visualization of structural and perfusion
abnormalities in SSPE, far surpassing the capabilities of Gd-based
CAs. In vivo biosafety assessment in the pig model
confirmed the high biocompatibility of Mg 0.03 -USIOs. Our
findings provide a highly efficient doping strategy to construct high-performance
USIOs-based T 1 CAs for sensitive MRI of
microvascular structural and functional abnormalities.
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhengtao Xu,Chen Wang,Zhuangzhuang Zhao,Yuxin Zhang,Yao Ying,Juan Li,Liang Qiao,Jingwu Zheng,Shenglei Che,Jing Yu
Theranostic probes that integrate diagnosis and treatment together are considered as effective tools for individual therapy. However, the separation of detection and treatment components limits precise assessment of therapeutic efficacy. Herein, a novel self-monitoring probe that sensitively responds to adenosine triphosphate (ATP) was developed by ultrafine iron oxide nanowires (UIONWs) through an oleyl amine-assisted way. The UIONWs, with a diameter of 1.5 nm and length of 75 nm, are surface-coordinated with oleyl amine. UIONWs can be decomposed in ATP-containing solution and expose the shielded iron ions. Consequently, it can boost the peroxidase (POD) activity and activate the T 1 -magnetic resonance imaging (MRI) signal by ATP. In addition, UIONWs can be rapidly engulfed into cells due to the high aspect ratio. The improved ATP and hydrogen peroxide (H 2 O 2 ) within tumor cells leads to higher hydroxyl radicals (OH) generation for effective tumor inhibition.In contrast, normal cells exhibit lower ATP and H 2 O 2 levels, reducing cytotoxicity and ensuring safety. Since both the illumination of T 1 -MRI and OH generation are ATP-controlled, this work raised a potential way to self-monitor tumor therapy with timely feedback on therapeutic effects.
研究领域:
生物医学工程
·
纳米医学
·
影像医学
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产品关联
DOI
高影响因子
MAGNETIC RESONANCE IN MEDICINE
·
2026
·
IF 3.2
Wenyan Zhang,Zelong Chen,Quan Tao,Caixia Li,Jianping Wang,Yizhe Zhang,Di Xie,Jianhua Ma,Thoralf Niendorf,Yanqiu Feng
Purpose To develop and validate dual breath-hold Look-Locker inversion recovery (Dual 3DLL) MRI for 3D whole-kidney T 1 quantification using dictionary matching. Methods Dual 3DLL employs two breath-hold Look-Locker prepared acquisitions using nonselective adiabatic inversion in conjunction with 3D balanced SSFP readouts at three inversion times for each breath-hold. Retrospective registration of T 1 -weighted images was implemented to reduce misalignment between two breath-holds. For T 1 quantification, Bloch equation-based dictionary matching was applied. Dual 3DLL was validated in phantoms using inversion recovery spin-echo (IRSE) based T 1 mapping as a reference and in 11 healthy subjects, where 2D MOLLI-based renal T 1 mapping was used as a reference. Results Validation in the phantom showed an agreement between Dual 3DLL and IRSE (precision: coefficient of variation = 2.5%, relative error compared to IRSE: 4.3% ± 2.0%). The human feasibility study demonstrated the clinical applicability of Dual 3DLL. Averaged T 1 derived from whole-kidney coverage Dual 3DLL was in accordance with that of 2D MOLLI (renal cortex: T 1,Dual 3DLL = 1413.41 ± 114.73 ms, T 1,MOLLI = 1394.39 ± 58.01 ms; medulla: T 1,Dual 3DLL = 1827.48 ± 108 ms, T 1,MOLLI = 1843.67 ± 91.54 ms). The coefficients of variation between T 1 obtained from Dual 3DLL and MOLLI were 6.1% for the renal cortex and 4.4% for the medulla. Conclusion This study demonstrates the feasibility of 3D whole kidney T 1 mapping using dual breath-hold Look-Locker T 1 -weighting in conjunction with balanced SSFP readouts and dictionary matching, and provides a technical foundation for improving our understanding of renal (patho-)physiology.
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Jinhong Hou,Hongqian Liu,Qian Ma,Suying Xu,Leyu Wang
Accurate diagnosis of diseases located in deep tissues is always challenging. The “always-on” probe often leads to false-positive signals due to nonspecific interaction of nanoprobes. Thus, stimuli-responsive nanoprobes are highly desirable, which, however, require complicated surface modification so as to achieve trigger-induced signal changes. Here pH-triggered switchable magnetic resonance imaging (MRI) nanoprobes were constructed by coordination-driven self-assembly of monodispersed iron oxide nanoparticles (MIONPs) with simple amino acid derivatives, which displayed typical T2-weighted MRI features, yet, were turned into T1-weighted MRI under slightly acidic conditions at the tumor site. The dynamic assembly and disassembly properties of MIONPs afford T2/T1 switchable contrast imaging, enabling selective “turn-on” signals at the tumor site with high specificity.
研究领域:
纳米技术
·
生物医学工程
·
医学影像
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）