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Analytical Methods · 2017 ·Vol. 9 ·期 21 ·3099-3104 · IF 1.9

BSA directed-synthesis of biocompatible Fe3O4 nanoparticles for dual-modal T1 and T2 MR imaging in vivo

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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BIOMEDICINE & PHARMACOTHERAPY · 2022 · IF 7.419

Magnetic vortex nanoring coated with gadolinium oxide for highly enhanced T1-T2 dual-modality magnetic resonance imaging-guided magnetic hyperthermia cancer ablation

Jianfeng Bao,Shuangshuang Guo,Xiangyang Zu,Yuchuan Zhuang,Dandan Fan,Yong Zhang,Yupeng Shi,Xin Pang,Zhenyu Ji,Jingliang Cheng

Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe 3 O 4 @Gd 2 O 3 , abbreviated as VNFG) was firstly designed and prepared for highly enhanced T 1 -T 2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG’s biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 磁共振成像
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 43 ·9055-9066 · IF 6.331

EDTMP ligand-enhanced water interactions endowing iron oxide nanoparticles with dual-modal MRI contrast ability

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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Biomedical Materials · 2021 ·Vol. 16 ·期 4 ·044104 · IF 3.715

Highly sensitive T 1–T 2 dual-mode MRI probe based on ultra-small gadolinium oxide-decorated iron oxide nanocrystals

Yashuang Miao,Peirong Chen,Miao Yan,Jianmin Xiao,Biao Hong,Ke Zhou,Guilong Zhang,Junchao Qian,Zhengyan Wu

Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficient T1–T2 dual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15% (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently, T1 and T2 values of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo sequence, respectively. Based on this, T1 and T2 relaxivities of GMIO-2 were calculated and were the highest (r1: 1.306 m M−1 s−1 and r2: 234.5 m M−1 s−1) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellent T1–T2 dual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of a T1–T2 dual-mode MRI CA.

研究领域: 医学影像 · 纳米技术 · 材料科学 · 生物医学工程
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-12 · IF 17.694

A pH-responsive T1-T2 dual-modal MRI contrast agent for cancer imaging

Lu Hongwei,Chen An,Zhang Xindan,Wei Zixiang,Cao Rong,Zhu Yi,Lu Jingxiong,Wang Zhongling,Tian Leilei

Magnetic resonance imaging (MRI) is a non-invasive imaging technology to diagnose health conditions, showing the weakness of low sensitivity. Herein, we synthesize a contrast agent, SPIO@SiO 2 @MnO 2 , which shows decreased T 1 and T 2 contrast intensity in normal physiological conditions. In the acid environment of tumor or inflamed tissue, the manganese dioxide (MnO 2 ) layer decomposes into magnetically active Mn 2+ (T 1 -weighted), and the T 1 and T 2 signals are sequentially recovered. In addition, both constrast quenching-activation degrees of T 1 and T 2 images can be accurately regulated by the silicon dioxide (SiO 2 ) intermediate layer between superparamagnetic iron oxide (SPIO) and MnO 2 . Through the “dual-contrast enhanced subtraction” imaging processing technique, the contrast sensitivity of this MRI contrast agent is enhanced to a 12.3-time difference between diseased and normal tissue. Consequently, SPIO@SiO 2 @MnO 2 is successfully applied to trace the tiny liver metastases of approximately 0.5 mm and monitor tissue inflammation.

研究领域: 医学影像 · 癌症研究 · 材料科学 · 生物医学工程
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Journal of Materials Chemistry B · 2024 · IF 6.1

Polymeric 1H/19F Dual-modal MRI Contrast Agent with Snowman-like Janus Nanostructure

Ziwei Duan,Jialei Han,Yadong Liu,Xinyu Zhao,Bo Wang,Shuaishuai Cao,Dalin Wu

Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinical, however, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with 19F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (r1) compared to gadolinium. Dual-modal imaging, combining 1H and 19F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized via seeded emulsion polymerization and post-modification. J-CA demonstrates excellent in vitro and in vivo performance in both 19F and 1H MRI, with T2 relaxation time of 5 ms and r1 of 0.31 mM-1·s-1, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.

研究领域: 医学诊断 · 磁共振成像 (MRI) · 造影剂 · 纳米技术 · 生物医学工程
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Scientific Reports · 2024 ·Vol. 14 ·期 1 ·10646-10646 · IF 3.8

Ultrasmall Fe3O4 nanoparticles self-assembly induced dual-mode T1/T2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics.

Qinghua Xie,Xuemei Wang,Gaorui Zhang,Dawei Zhou,Yuxuan Zhao,Hong Liu,Jiazhi Duan,Dexin Yu,Yuanhua Sang

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe 3 O 4 nanoclusters were developed for tumor-targeted dual-mode T 1 /T 2 -weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe 3 O 4 nanoclusters synthesized by facilely modifying ultrasmall Fe 3 O 4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe 3 O 4 nanoclusters shows excellent dual-mode T 1 and T 2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe 3 O 4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe 3 O 4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.

CAS / MDL: 27599-63-9
研究领域: 纳米技术 · 生物医学工程 · 分子影像 · 癌症治疗 · 材料科学
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ACS Applied Nano Materials · 2020 · IF 0

Synthesis of Ultrasmall Fe3O4 Nanoparticles as T1–T2 Dual-Modal Magnetic Resonance Imaging Contrast Agents in Rabbit Hepatic Tumors

Chen Bai,Pengcheng Hu,Nianlong Liu,Guodong Feng,Di Liu,Yi Chen,Ming Ma,Ning Gu,Yu Zhang

To elevate the accurate diagnosis of tumors, nanomaterial-based magnetic resonance imaging (MRI) contrast agents are being rapidly developed. In this paper, we report the large-scale synthetic method of Fe3O4 nanoparticles by high-temperature thermal decomposition and their application as time-dependent T1–T2 dual-modal MRI contrast agents in rabbit hepatic tumors. The Fe3O4 nanoparticles are modified with bull serum albumin (BSA), which provides excellent biocompatibility and colloidal stability. These nanoparticles also exhibit a high r1 value of 6.99 mM–1 s–1 and a low r2 value of 24.11 mM–1 s–1 at a clinically relevant magnetic field (3.0 T). In in vivo experiments, after intravenous administration with these nanoparticles, the rapid T2-weighted effect can be acquired within 5 min and the slow T1 contrast enhancement at the tumor site appears at 90 min. The explanation of this phenomenon is possibly due to the different accumulation rates and states of the nanoparticles in different tissues. In normal liver tissue, the nanoparticles can be quickly phagocytosed by a reticuloendothelial system and accumulated in the liver. These accumulated nanoparticles aggregate, improving the T2-weighted effect and reducing the T1-weighted effect. However, because of an enhanced permeation and retention effect, the nanoparticles are delivered into tumor tissue gradually and dispersedly, which takes a longer time to generate the T1-weighted effect at the tumor site. In summary, these Fe3O4 nanoparticles have significant potential to improve the diagnostic accuracy and sensitivity in MRI.

CAS / MDL: 67-68-5
研究领域: 纳米技术 · 医学成像 · 生物医学工程 · 癌症研究 · 药理学
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