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ADVANCED MATERIALS · 2024 ·Vol. 36 ·期 29 ·2401538 · IF 27.4

Structural Defect-Enabled Magnetic Neutrality Nanoprobes for Ultra-High-Field Magnetic Resonance Imaging of Isolated Tumor Cells in Vivo

Hui Du,Qiyue Wang,Bo Zhang,Zeyu Liang,Canyu Huang,Dao Shi,Fangyuan Li,Daishun Ling

The identification of metastasis “seeds,” isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T 2 -decaying effects under UHF conditions, which compromises T 1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T 2 -decaying effect while concurrently enhancing UHF T 1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r 2 / r 1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.

研究领域: 医学影像学 · 肿瘤学
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Nature Communications · 2021 ·Vol. 12 ·期 1 ·1-11 · IF 14.919

Artificially engineered antiferromagnetic nanoprobes for ultra-sensitive histopathological level magnetic resonance imaging

Liang Zeyu,Wang Qiyue,Liao Hongwei,Zhao Meng,Lee Jiyoung,Yang Chuang,Li Fangyuan,Ling Daishun

Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities. Recent development of ultra-high-field (UHF) magnetic resonance imaging (MRI) represents a large step toward this goal. Nevertheless, there is a lack of proper contrast agents that can provide superior imaging sensitivity at UHF for disease detection, because conventional contrast agents generally induce T2 decaying effects that are too strong and thus limit the imaging performance. Herein, by rationally engineering the size, spin alignment, and magnetic moment of the nanoparticles, we develop an UHF MRI-tailored ultra-sensitive antiferromagnetic nanoparticle probe (AFNP), which possesses exceptionally small magnetisation to minimize T2 decaying effect. Under the applied magnetic field of 9 T with mice dedicated hardware, the nanoprobe exhibits the ultralow r 2 / r 1 value (~1.93), enabling the sensitive detection of microscopic primary tumours (<0.60 mm) and micrometastases (down to 0.20 mm) in mice. The sensitivity and accuracy of AFNP-enhanced UHF MRI are comparable to those of the histopathological examination, enabling the development of non-invasive visualization of previously undetectable biological entities critical to medical diagnosis and therapy.

研究领域: 医学成像 · 纳米技术 · 生物医学工程 · 肿瘤学
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Acta Biomaterialia · 2023 · IF 9.7

Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy

Ruling Zhang,Meng Liu,Sitong Liu,Xiaotong Liang,Ruitao Lu,Xintao Shuai,Dalin Wu,Zhong Cao

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T 1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T 2 -weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10 −13 s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. Statement of significance Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T 1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T 2 MRI properties (r 2 = 152.13 mM −1 s −1 ) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.

CAS / MDL: 62-31-7 108-67-8
研究领域: 医学成像 · 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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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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