Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou 310009, China.
Department of Radiology, Lishui Hospital of Zhejiang University , Lishui 323000, China.
ACS Appl Mater Interfaces. 2017 Oct 18;9(41):35548-35561. doi: 10.1021/acsami.7b09879. Epub 2017 Oct 4.
Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.
如今,人们对用于肝癌早期诊断的超高灵敏度对比剂有很高的需求。人们已经认识到,通过构建肝脏肿瘤特异性靶向探针,可以获得准确的成像信息,尽管这仍然面临挑战。在这里,首次制备了一种 AGKGTPSLETTP 肽(A54)功能化超顺磁性氧化铁(SPIO)负载的纳米结构脂质载体(A54-SNLC),它可以被肝癌细胞(Bel-7402)特异性摄取,并在 T2 加权成像(T2WI)上表现出随铁浓度变化的超低成像信号强度。然后,设计了一种具有肿瘤特异性启动子(AFP 启动子)的内源性铁蛋白报告基因用于磁共振成像(MRI),它也可以在 T2WI 上显示信号强度降低。最后,使用鱼精蛋白作为阳离子介导物,实现了新型 A54-SNLC/鱼精蛋白/DNA(A54-SNPD)三元纳米颗粒作为主动双重靶向 T2 加权 MRI 造影剂用于肝肿瘤成像。由于 A54-SNLC 和 AFP 促进的 DNA 与 Bel-7402 细胞的靶向协同作用,通过三元纳米粒子的 T2 对比增强成功降低了肝肿瘤的 T2 成像强度值。值得强调的是,新型 A54-SNPD 三元纳米颗粒作为主动双重靶向 T2 加权 MRI 造影剂能够大大提高肝癌的诊断灵敏度和特异性。
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