P-Selectin-Based Dual-Model Nanoprobe Used for the Specific and Rapid Visualization of Early Detection toward Severe Acute Pancreatitis in Vivo,ACS Biomaterials Science & Engineering

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P-Selectin-Based Dual-Model Nanoprobe Used for the Specific and Rapid Visualization of Early Detection toward Severe Acute Pancreatitis in Vivo
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-09-14 , DOI: 10.1021/acsbiomaterials.0c00596
Lingli Long _{1,

2} , Lingna Deng ₂ , Liqin Wang ₃ , Shihong Wen ₄ , Liang Luo ₅ , Liqun Liang ₆ , Lu Ding ₂ , Jianfeng Wu ₆ , Zhizhong Ye ₇ , David Y. B. Deng _{1,

2}

Affiliation

Identifying severe acute pancreatitis (SAP) as soon as possible is critical for achieving optimal outcomes and saving lives. In this study, a novel P-selectin-targeted, NIR fluorescent dye (Cy 5.5)-labeled dual-modal nanoprobe based on diethylenetriaminepentaacetic chelates (Gd-DTPA-Cy5.5-PsLmAb) was constructed for the bimodal imaging of SAP at the early stage. Gd-DTPA-Cy5.5-PsLmAb was prepared, and its structure was characterized by Fourier transform infrared spectroscopy, UV–vis spectroscopy, and fluorescence spectroscopy, and its stability was evaluated. Biocompatibility was evaluated by the hemolysis and cytotoxicity assays. The enzyme-linked immunosorbent assay was used to detect and evaluate the expression of P-selectin in the peripheral blood of 11 patients with acute pancreatitis (AP) and 5 healthy volunteers. The bimodal imaging ability of Gd-DTPA-Cy5.5-PsLmAb nanoprobes was evaluated via near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI) in AP animal models in vivo. Gd-DTPA-Cy5.5-PsLmAb showed low toxicity to human embryonic kidney cells (293T cells) and good blood compatibility. The P-selectin levels of humans and rats in the mild acute pancreatitis (MAP)/SAP stage were significantly higher than those in the control group and reached the highest level at the SAP stage. Furthermore, Gd-DTPA-Cy5.5-PsLmAb nanoprobes showed clear NIRF imaging of mouse pancreas at the MAP stage and SAP stage by a fluorescence signal at 6.09 × 10⁸ and 1.95 × 10⁹, respectively. Meanwhile, Gd-DTPA-Cy5.5-PsLmAb nanoprobes also successfully showed the T1-weighted MR signal of rat pancreas at the MAP stage, but Gd-DTPA seldom showed any signal increase at the MAP stage; Gd-DTPA-Cy5.5-PsLmAb and Gd-DTPA could show an increasing MR signal of rat pancreas at the SAP stage. Gd-DTPA-Cy5.5-PsLmAb proved to offer a stronger signal than Gd-DTPA.Our findings indicate that Gd-DTPA-Cy5.5-PsLmAb is an effective and specific MR/NIRF dual nanoprobe for bimodal imaging, providing a promising diagnostic approach for early SAP in clinic.

中文翻译：

基于P-选择蛋白的双模型纳米探针用于对严重急性胰腺炎的体内早期检测的特异性和快速可视化

尽早发现严重急性胰腺炎（SAP）对于获得最佳结果和挽救生命至关重要。在这项研究中，基于二亚乙基三胺五乙酸螯合物（Gd-DTPA-Cy5.5-PsLmAb）的新型P-选择素靶向NIR荧光染料（Cy 5.5）标记的双峰纳米探针被构建用于SAP的双峰成像。早期。制备了Gd-DTPA-Cy5.5-PsLmAb，并通过傅里叶变换红外光谱，紫外-可见光谱和荧光光谱对其结构进行了表征，并对其稳定性进行了评估。通过溶血和细胞毒性试验评估生物相容性。酶联免疫吸附试验用于检测和评估11例急性胰腺炎（AP）患者和5名健康志愿者的外周血中P-选择素的表达。体内。Gd-DTPA-Cy5.5-PsLmAb对人胚胎肾细胞（293T细胞）毒性低，血液相容性好。在轻度急性胰腺炎（MAP）/ SAP阶段，人和大鼠的P-选择素水平显着高于对照组，并在SAP阶段达到最高水平。此外，Gd-DTPA-Cy5.5-PsLmAb纳米探针通过6.09×10 ⁸和1.95×10 ⁹的荧光信号显示了在MAP和SAP阶段小鼠胰腺的清晰NIRF成像。，分别。同时，Gd-DTPA-Cy5.5-PsLmAb纳米探针在MAP阶段也成功显示了大鼠胰腺的T1加权MR信号，但Gd-DTPA在MAP阶段很少显示任何信号增加。Gd-DTPA-Cy5.5-PsLmAb和Gd-DTPA可能在SAP阶段显示大鼠胰腺的MR信号增加。经证实，Gd-DTPA-Cy5.5-PsLmAb比Gd-DTPA提供更强的信号。我们的发现表明，Gd-DTPA-Cy5.5-PsLmAb是一种有效且特异的MR / NIRF双纳米探针，可用于双峰成像。临床早期SAP的诊断方法。

更新日期：2020-10-12

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