Zhang Deliang, Zhuang Rongqiang, Li Jindian, Lv Yuting, Yang Xia, Pan Weimin, Zhang Xianzhong
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
Department of Nuclear Medicine, Xiang'an Hospital Affiliated to Xiamen University, Xiamen 361102, China.
Mol Pharm. 2021 Nov 1;18(11):4140-4147. doi: 10.1021/acs.molpharmaceut.1c00545. Epub 2021 Oct 16.
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. Tc-labeled -acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with Tc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of Tc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of Tc-NAG-PEI in the NAG-PEI/TGF-β1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of Tc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.
特发性肺纤维化（IPF）是一种预后不良的进行性纤维化疾病。证据表明，波形蛋白是肺纤维化形成的关键调节因子。本研究中，将锝标记的N-乙酰葡糖胺-聚乙烯亚胺（NAG-PEI），一种靶向波形蛋白的放射性示踪剂，用于IPF的早期诊断，并且NAG-PEI还用作治疗IPF的治疗性小干扰RNA（siRNA）递送载体。用锝标记的NAG-PEI对博来霉素（BM）和二氧化硅诱导的IPF小鼠进行单光子发射计算机断层扫描（SPECT）成像，以可视化肺纤维化并监测负载siRNA的NAG-PEI、脂多糖（LPS，一种耐受性佐剂）或酵母聚糖（ZYM，一种免疫刺激剂）的治疗效果。BM和二氧化硅诱导的IPF小鼠中锝-NAG-PEI的肺摄取与IPF进展明显直接相关。NAG-PEI/TGF-β1-siRNA治疗组或LPS治疗组中锝-NAG-PEI的肺摄取明显低于对照组，而ZYM治疗组中锝-NAG-PEI的肺摄取明显高于对照组。这些结果表明，NAG-PEI是一种用于IPF诊断和治疗强大的微SPECT成像引导的诊疗平台。
