A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging

Zhang, Huan; Guo, Yingkun; Jiao, Ju; Qiu, Ying; Miao, Yuqing; He, Yuan; Li, Zhenlin; Xia, Chunchao; Li, Li; Cai, Jing; Xu, Ke; Liu, Xiaoli; Zhang, Ce; Bay, Boon‐Huat; Song, Shijie; Yang, Yanlian; Peng, Mingli; Wang, Yao‐Yu; Fan, Hai

doi:10.1038/s41551-022-00975-2

Cited by 49 publications

(36 citation statements)

References 65 publications

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“…Generally, HCC has low to non-OATP expression, by which T 1 -weighted MRI is able to diagnose HCC by viewing the contrast distinction between the tumor and normal hepatocyte with the aid of hepatic-specific GBCAs. , An orthotopic HCC model was built by implanting the HuH7 tumor to the livers of normal BALB/c mice in order to testify the applicability of Gd-L 3 and Gd-L 4 in the diagnosis of liver tumor. According to the axial images of liver in Figures A,B and S9, the tumor sites were invisible, while a clear contrast was observed after hepatocellular uptake of both complexes.…”

Section: Resultsmentioning

confidence: 99%

Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

et al. 2023

J. Med. Chem.

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The safety risks of gadolinium (Gd 3+ )-based contrast agents (GBCAs) arise from their inevitable leakage of Gd 3+ , and the pursuit of more stable GBCAs for magnetic resonance imaging (MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTA are the only two authorized GBCAs for liver diagnosis in spite of their weak stability. In this study, one of the pendent arms of the most inert commercial Gd-DOTA was decorated with phenyl moieties, in which obvious enhancements of both kinetic and thermodynamic stability were achieved. Gd-L 4 with a para-substituted OBn group was observed with ready hepatocellular uptake, with significant contrast provided in diagnosing orthotopic hepatocellular carcinoma, and its hepatobiliary secretion accounted for more than 50% of the injection dose in mice. In this study, Gd-L 4 was found with comparable performance in liver MRI diagnosis to that of commercial Gd-EOB-DTPA and was thus deemed as an ideal candidate for further clinical applications.

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Section: Resultsmentioning

confidence: 99%

Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

et al. 2023

J. Med. Chem.

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“…Yet, currently there are only two task-specific CAs for liver diagnostic applications, i.e., Gd-EOB-DTPA and Gd-BOPTA, but facing risks of Gd 3+ leakage due to their poor inertness. Many mimics of Gd-EOB-DTPA have been reported by combining the lipophilic ethoxybenzyl (EOB) group with chelate skeletons including DO3A, , PyC2A, and even nanoparticles . Besides, difficulties aroused commonly in discrimination between normal tissue and lesions such as solid tumors, as common GBCAs have no significant difference in extravasation between them .…”

Section: Introductionmentioning

confidence: 99%

Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents

Xu,

Ye,

et al. 2023

J. Med. Chem.

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The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.

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“…This accumulation pattern leads to a distinct "dark" appearance in the tumor region. 38,39 Over time, the liver tumors became progressively darker, and the boundary between liver tumors and normal liver tissues was more prominent in the WO 3−x NPs-injected group (R-W) compared to the iopromide-injected group (R-I). The sections where tumor tissues and normal liver tissues merge together were marked out by red lines.…”

Section: In Vivo Dect Imaging With Wo 3−x Npsmentioning

confidence: 99%

Tungsten-based nanoparticles as contrast agents for liver tumor detection using dual-energy computed tomography

Ji,

Zhu,

Hsu

et al. 2023

Biomater. Sci.

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A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging

Cited by 49 publications

References 65 publications

Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging

Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents

Tungsten-based nanoparticles as contrast agents for liver tumor detection using dual-energy computed tomography

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