Gadolinium-loaded calcium phosphate nanoparticles for magnetic resonance imaging of orthotopic hepatocarcinoma and primary hepatocellular carcinoma.,Biomaterials Science

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Gadolinium-loaded calcium phosphate nanoparticles for magnetic resonance imaging of orthotopic hepatocarcinoma and primary hepatocellular carcinoma.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020/01/23 , DOI: 10.1039/c9bm01544b
Nan-Nan Zhang ₁ , Chen-Ying Lu ₁ , Gao-Feng Shu ₁ , Jie Li ₁ , Min-Jiang Chen ₁ , Chun-Miao Chen ₁ , Xiu-Ling Lv ₂ , Xiao-Ling Xu ₃ , Wei Weng ₂ , Qiao-You Weng ₁ , Bu-Fu Tang ₁ , Yong-Zhong Du ₃ , Jian-Song Ji ₁

Affiliation

The development of magnetic resonance imaging (MRI) contrast agents with high sensitivity and good biocompatibility is of great value for the diagnosis of primary hepatocellular carcinoma (HCC). Here, a novel MRI contrast agent based on calcium phosphate (CaP) nanoparticles modified with a liver cancer cell targeting peptide A54 (A54-CaP) was fabricated. The T1-positive contrast agent Gd-DTPA was encapsulated inside the nanoparticles (A54-CaPNPs), with a mean diameter of 30 nm and a high encapsulation efficiency of 92.73%. The A54-CaPNP solution exhibited higher longitudinal relaxivity (6.07 mM-1 s-1) than that of the clinically used MRI contrast agent Gd-DTPA (3.56 mM-1 s-1). A much higher accumulation of the nanoparticles in the liver cells was observed, which was directed by the A54 targeting peptide. Furthermore, the MRI diagnostic efficiency of A54-CaPNPs was systematically investigated in an orthotopic liver cancer model and primary HCC model. In vivo MRI experiments showed that A54-CaPNPs had higher sensitivity in the BEL-7402 orthotopic liver cancer model with a more remarkable contrast enhancement and a longer imaging time compared to those without A54 modification. Moreover, the experiments on primary HCC models suggested that A54-CaPNPs showed greatly enhanced MR imaging performance in comparison with Gd-DTPA. These results suggest that A54-CaPNPs possess great potential to enable the non-invasive early diagnosis of primary HCC for timely surgical resection.

中文翻译：

负载d的磷酸钙纳米粒子用于原位肝癌和原发性肝细胞癌的磁共振成像。

具有高灵敏度和良好生物相容性的磁共振成像（MRI）造影剂的开发对原发性肝细胞癌（HCC）的诊断具有重要价值。在这里，基于肝细胞靶向肽A54（A54-CaP）修饰的磷酸钙（CaP）纳米粒子，制造了一种新型MRI造影剂。T1阳性造影剂Gd-DTPA被封装在纳米粒子（A54-CaPNPs）内，平均直径为30 nm，封装效率高达92.73％。与临床使用的MRI造影剂Gd-DTPA（3.56 mM-1 s-1）相比，A54-CaPNP溶液具有更高的纵向松弛度（6.07 mM-1 s-1）。观察到纳米颗粒在肝细胞中的积累更高，这是由A54靶向肽指导的。此外，在原位肝癌模型和原发性肝癌模型中，系统地研究了A54-CaPNPs的MRI诊断效率。体内MRI实验表明，与未经A54修饰的患者相比，A54-CaPNPs在BEL-7402原位肝癌模型中具有更高的敏感性，并具有更显着的对比度增强和更长的成像时间。此外，对原发性肝癌模型的实验表明，与Gd-DTPA相比，A54-CaPNPs显示出大大增强的MR成像性能。这些结果表明，A54-CaPNP具有巨大的潜力，可以无创地早期诊断原发性肝癌，以便及时进行手术切除。体内MRI实验表明，与未经A54修饰的患者相比，A54-CaPNPs在BEL-7402原位肝癌模型中具有更高的敏感性，并具有更显着的对比度增强和更长的成像时间。此外，对原发性肝癌模型的实验表明，与Gd-DTPA相比，A54-CaPNPs显示出大大增强的MR成像性能。这些结果表明，A54-CaPNP具有巨大的潜力，可以无创地早期诊断原发性肝癌，以便及时进行手术切除。体内MRI实验表明，与未经A54修饰的患者相比，A54-CaPNPs在BEL-7402原位肝癌模型中具有更高的敏感性，并具有更显着的对比度增强和更长的成像时间。此外，对原发性肝癌模型的实验表明，与Gd-DTPA相比，A54-CaPNPs显示出大大增强的MR成像性能。这些结果表明，A54-CaPNP具有巨大的潜力，可以无创性地早期诊断原发性肝癌，以便及时进行手术切除。

更新日期：2020-03-31

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