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T1-T2双模态
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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MOLECULES · 2023 ·Vol. 28 ·期 16 ·6134 · IF 4.6

cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1–T2 Dual-Modal MRI and DTX Delivery

Shengchao Wang,Guiqiang Qi,Zhichen Zhang,Qiangqiang Yin,Na Li,Zhongtao Li,Guangyue Shi,Haifeng Hu,Liguo Hao

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1–T2dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.Keywords:T1–T2;DTX;MRI;drug delivery;pancreatic cancer

研究领域: 医学影像学 · 纳米技术 · 肿瘤学 · 药物递送系统
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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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BIOMATERIALS · 2015 · IF 8.557

Polydopamine-based coordination nanocomplex for T1/T2 dual mode magnetic resonance imaging-guided chemo-photothermal synergistic therapy

Yan Chen,Kelong Ai,Jianhua Liu,Xiaoyan Ren,Chunhuan Jiang,Lehui Lu

Despite the progress in the design and synthesis of theranostic agents, limitations on efficiency and safety offer significant room for improvement in these agents. Inspired by the natural binding ability of polydopamine nanospheres (PDAs) with iron ion , a simple and versatile synthesis strategy is developed to prepare biodegradable coordination polymer (CP) encapsulated PDAs nanocomplex ( [email protected] x , x = 3, 6, 9). We found that the [email protected] 3 can serve as a T 1 /T 2 dual mode contrast agent (DMCA) for magnetic resonance imaging (MRI), which possesses high longitudinal (r 1  = 7.524 mM −1  s −1 ) and transverse (r 2  = 45.92 mM −1  s −1 ) relaxivities. In this system, benefitting from the high photothermal conversion efficiency derived from PDAs, DOX loaded [email protected] 3 nanocomplex is able to not only destroy the tumor directly by heat, but also stimulate the chemotherapy by enabling NIR-responsive on demand delivery of DOX. To the best of our knowledge, this is the first example exploring the potential of [email protected] x nanocomplex for T 1 /T 2 dual mode MRI-guided chemo-photothermal synergistic therapy. This work extends the currently available theranostic agents, and opens up new avenues to rationally design the high-performance T 1 /T 2 DMCA.

CAS / MDL: 554-95-0
研究领域: 纳米医学 · 核磁共振成像 · 癌症治疗 · 材料科学
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Biomaterials Science · 2022 ·Vol. 10 ·期 18 ·5254-5264 · IF 7.59

Tumor-penetrating iron oxide nanoclusters for T1/T2 dual mode MR imaging-guided combination therapy

Jing Li,Siman Gong,Shiyu Li,Xinchong Li,Siyi Lan,Minjie Sun

Emerging nanotheranostic systems have promoted the development of dual-mode imaging techniques (i.e. T1/T2-weighted MRI) to meet the increasing requirements of accurate personalized treatment for cancer. Nevertheless, slight tumor accumulation and poor penetration have limited the efficacy of dual-mode theranostic agents. Furthermore, under the premise of guaranteeing imaging capability, most current research studies hardly focused on optimizing theranostic agents to achieve considerable therapeutic effects. Here, we developed a hyaluronic acid (HA)-stabilized iron oxide nanocluster (Fe2O3@PFDH NC) as an intelligent-degradable theranostic nanoagent for dual-mode MRI-guided chemo-photothermal therapy. The obtained Fe2O3@PFDH NC with high longitudinal and transverse relaxivities offers strong contrast in T1/T2-weighted MR imaging. Meanwhile, according to MR images, the intravenous Fe2O3@PFDH NC could accumulate at the hyaluronidase-rich tumor location gradually. More interestingly, it could break into smaller nanoparticles with quick DOX release for deep penetration, accompanied by highly effective photothermal ablation of the tumor under laser irradiation. In conclusion, the versatile tumor-penetrating Fe2O3@PFDH nanocluster could serve as a T1/T2 dual-mode MRI contrast agent with highly effective combination chemo-photothermal therapy, and would be an ideal theranostic nanocarrier with translational potential for future clinical diagnosis and treatment of cancer.

研究领域: 纳米医学 · 癌症诊疗学 · 核磁共振成像 · 材料科学
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Biomaterials Science · 2021 ·Vol. 9 ·期 22 ·7591-7602 · IF 6.843

An intelligent tumor microenvironment responsive nanotheranostic agent for T1/T2 dual-modal magnetic resonance imaging-guided and self-augmented photothermal therapy

Junlie Yao,Fang Zheng,Fang Yang,Chenyang Yao,Jie Xing,Zihou Li,Sijia Sun,Jia Chen,Xiawei Xu,Yi Cao,Norbert Hampp,Aiguo Wu

Photothermal therapy (PTT), as a promising antineoplastic therapeutic strategy, has been harnessed to restrain tumor growth through near-infrared (NIR) irradiation mediated thermal ablation. Nevertheless, its biological applications are hampered by thermal diffusion and up-regulated heat shock proteins (HSPs). Herein, a versatile nanotheranostic agent is developed via integrating Zn0.2Fe2.8O4 nanoparticles (NPs), polydopamine (PDA), and MnO2 NPs for T1/T2 dual-modal magnetic resonance (MR) imaging-guided and self-augmented PTT. The as-designed Zn0.2Fe2.8O4@PDA@MnO2 NPs adequately serve as a PTT agent to realize effective photothermal conversion and obtain local hyperthermia. Additionally, the Zn0.2Fe2.8O4@PDA@MnO2 NPs can significantly consume overexpressed glutathione (GSH) and generate Mn2+ in the tumor microenvironment (TME), thus destroying redox homeostasis and catalytically generating hydroxyl radicals (˙OH) for HSP suppression and PTT enhancement. Meanwhile, Mn2+ and Zn0.2Fe2.8O4 NPs significantly strengthen T1- and T2-weighted MR contrast for tumor imaging and PTT guidance. Hence, this study offers proof of concept for self-augmented PTT and T1/T2 dual-modal MR imaging for tumor elimination.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 医学影像
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ACS Nano · 2024 · IF 15.8

Biomineralization Synthesis of HoMn Nanoparticles for Ultrahigh-Field-Tailored and T1–T2 Dual-Mode MRI-Guided Cancer Theranostics

Qingqing Cheng,Yanzhou Chang,Dong Zhang,Xiangsheng Zhao,Zeyu Xiao,Tianfeng Chen,Changzheng Shi,Liangping Luo

Ultrahigh field magnetic resonance imaging (UHF-MRI) (≥7 T) can dramatically boost image resolution and signal-to-noise ratio, which have distinct advantages in multifunctional imaging. However, their research and application are currently limited by the absence of high-field contrast agents (CAs) and the low sensitivity and accuracy of T1/T2 single-modality CAs. Therefore, the development of T1–T2 dual-mode CAs that respond to UHF-MRI and nanoformulations with therapeutic sensitization can bring ideas for the integrated application of precise and synchronous tumor theranostics. Herein, we present a biomimetic mineralization strategy for synthesizing holmium/manganese oxide–bovine serum albumin–photosensitizer chlorin e6 nanohybrids. The hybrid nanoparticles exhibited better tumor accumulation, a suitable time imaging window, and excellent pH-response T1–T2 dual-mode UHF-MRI performance. The antitumor effect comes from the amelioration of the hypoxic tumor microenvironment to promote the synergistic effect of photodynamic therapy and radiotherapy, along with negligible acute toxicity. Undoubtedly, this work not only provides a different perspective for developing multifunctional nanotherapeutics but also promotes the potential clinical exploitation and translation of UHF CAs.

研究领域: 纳米技术 · 磁共振成像 · 癌症诊疗学 · 材料科学 · 生物医学工程
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