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一种用于检测关节软骨损伤的新型磁共振成像造影剂NaGdF@PEG-CLS@MMP-13纳米粒子

A novel MRI contrast agent NaGdF@PEG-CLS@MMP-13 NPs for detecting articular cartilage injury.

作者信息

Xu Jian, Zhang Yijun, Lin Mao, Ma Binbin, He Hongpu, Jiang Fangyi, He Shukun, Yuan Chengjie

机构信息

Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.

Key Laboratory of Big Data for Spinal Deformities, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.

出版信息

Sci Rep. 2025 Feb 20;15(1):6251. doi: 10.1038/s41598-025-89444-9.

DOI:10.1038/s41598-025-89444-9
PMID:39979429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11842704/
Abstract

Early detection of cartilage injuries is crucial due to their limited self-repair capacity and risk of joint dysfunction. Conventional contrast agents like gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) offer low specificity and T1 relaxivity (r1), limiting MRI application. This study introduces NaGdF nanoparticles (NPs) modified with polyethylene glycol (PEG) and cholesterol (CLS) to enhance hydrophilicity and lipophilicity. Targeting is achieved using a matrix metalloproteinase-13 (MMP13) cartilage-binding peptide. NaGdF@PEG-CLS@MMP13 CBP NPs demonstrate an increased r1 value (8.07 mM s) compared to NaGdF@PEG-CLS NPs (6.65 mM s) and Gd-DTPA (3.01 mM s), enabling deeper cartilage penetration and stronger cartilage affinity. Two hours post-injection, these NPs improved the signal-to-noise ratio at injury sites by 2.4-fold over pre-injection values. Biocompatibility was confirmed with no adverse effects in blood or organs, and the NPs were metabolized in kidneys and liver, with excretion via urine. This study supports NaGdF@PEG-CLS@MMP13 CBP NPs as an effective MRI contrast agent, enhancing early detection of cartilage injuries.

摘要

由于软骨损伤的自我修复能力有限且存在关节功能障碍的风险，因此早期检测至关重要。像钆-二乙烯三胺五乙酸（Gd-DTPA）这样的传统造影剂特异性低且T1弛豫率（r1）低，限制了MRI的应用。本研究引入了用聚乙二醇（PEG）和胆固醇（CLS）修饰的NaGdF纳米颗粒（NPs），以增强亲水性和疏水性。使用基质金属蛋白酶-13（MMP13）软骨结合肽实现靶向。与NaGdF@PEG-CLS NPs（6.65 mM s）和Gd-DTPA（3.01 mM s）相比，NaGdF@PEG-CLS@MMP13 CBP NPs的r1值增加（8.07 mM s），能够实现更深的软骨穿透和更强的软骨亲和力。注射后两小时，这些纳米颗粒使损伤部位的信噪比相对于注射前的值提高了2.4倍。生物相容性得到证实，在血液或器官中没有不良反应，纳米颗粒在肾脏和肝脏中代谢，并通过尿液排泄。本研究支持NaGdF@PEG-CLS@MMP13 CBP NPs作为一种有效的MRI造影剂，可增强软骨损伤的早期检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/1c877c6c1379/41598_2025_89444_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/1c877c6c1379/41598_2025_89444_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/bcb9b59be4a2/41598_2025_89444_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/5c478fe4d60d/41598_2025_89444_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/b97cfddb974c/41598_2025_89444_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/4b0cbe870e49/41598_2025_89444_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/71670d073794/41598_2025_89444_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/04e024627e6c/41598_2025_89444_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c6a/11842704/1c877c6c1379/41598_2025_89444_Fig9_HTML.jpg

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