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靶向 PDGFB 的功能 MRI 纳米开关用于癌症的可激活 T-T 双模态超灵敏诊断。

PDGFB-targeted functional MRI nanoswitch for activatable T-T dual-modal ultra-sensitive diagnosis of cancer.

机构信息

School of Medical Imaging, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai, 264003, People's Republic of China.

Hefei Cancer Hospital, Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People's Republic of China.

出版信息

J Nanobiotechnology. 2023 Jan 6;21(1):9. doi: 10.1186/s12951-023-01769-7.

Abstract

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off-on T-T dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T-T dual-mode MRI signals. The tumor-specific off-on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off-on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.

摘要

作为目前应用最广泛的成像方式之一,磁共振成像(MRI)在癌症的临床精确诊断中得到了广泛应用。然而,低信噪比(SNR)和肿瘤特异性仍然是重大挑战。受距离相关磁共振调谐(MRET)现象的启发,本研究提出了肿瘤微环境(TME)激活的开-关 T-T 双模 MRI 纳米开关,以实现肿瘤的灵敏早期诊断。基于 PDGFB 修饰的氧化铁包覆 Mn 掺杂二氧化硅(PDGFB-FMS)设计并制造了肿瘤特异性纳米开关,它可以在 TME 中高浓度 GSH 和低 pH 条件下降解,从而激活 T-T 双模 MRI 信号。肿瘤特异性的开-关双模 MRI 纳米开关可显著提高 SNR,并成功用于早期肿瘤的精确诊断,尤其是用于原位前列腺癌。此外,纳米开关的全身给药不会引起血液或组织损伤,并且可以及时排出体外,表现出优异的生物安全性。总的来说,该策略是设计开-关双模 MRI 纳米探针以提高成像准确性的重要一步,为新型 MRI 探针的开发开辟了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/134c/9824934/c58d70a10c00/12951_2023_1769_Sch1_HTML.jpg

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