Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui 323000, China.
Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China.
Biomater Sci. 2020 Mar 31;8(7):1961-1972. doi: 10.1039/c9bm01544b.
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.
基于肝癌细胞靶向肽 A54 修饰的磷酸钙纳米粒子作为新型 MRI 对比剂用于原发性肝癌的诊断
开发具有高灵敏度和良好生物相容性的磁共振成像（MRI）对比剂对于原发性肝癌（HCC）的诊断具有重要价值。本研究构建了一种基于肝癌细胞靶向肽 A54 修饰的磷酸钙（CaP）纳米粒子的新型 MRI 对比剂（A54-CaP）。将 T1 阳性造影剂 Gd-DTPA 包封在纳米粒子内（A54-CaPNPs），平均粒径为 30nm，包封效率高达 92.73%。A54-CaPNP 溶液的纵向弛豫率（6.07mM-1s-1）高于临床应用的 MRI 造影剂 Gd-DTPA（3.56mM-1s-1）。观察到纳米颗粒在肝癌细胞中的积累明显增加，这是由 A54 靶向肽引导的。此外，还在原位肝癌模型和原发性 HCC 模型中系统研究了 A54-CaPNPs 的 MRI 诊断效率。体内 MRI 实验表明，与未修饰的 A54-CaPNPs 相比，A54-CaPNPs 在 BEL-7402 原位肝癌模型中具有更高的灵敏度，表现出更显著的对比增强和更长的成像时间。此外，原发性 HCC 模型的实验表明，与 Gd-DTPA 相比，A54-CaPNPs 显示出大大增强的磁共振成像性能。这些结果表明，A54-CaPNPs 具有很大的潜力，能够实现原发性 HCC 的非侵入性早期诊断，以便及时进行手术切除。
