Zhan Wenhua, Cai Xiaoxia, Li Hairui, Du Getao, Hu Hao, Wu Yayan, Wang Lin
Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University Xi'an 710049 Shaanxi China
Department of Radiation Oncology, General Hospital of Ningxia Medical University Yinchuan 750004 Ningxia China.
RSC Adv. 2020 Apr 3;10(23):13687-13695. doi: 10.1039/d0ra00897d. eCollection 2020 Apr 1.
Multidrug resistance (MDR) is a huge challenge for gastric cancer chemotherapy. Therefore, MDR accurate monitoring is of great significance for the treatment of gastric cancer. GMBP1, an extracellular internalization peptide, can target MDR gastric cancer cells through specific binding to GRP78, which is an MDR-related protein that is overexpressed in gastric cancer cells. Herein, we constructed GMBP1 conjugated MnO nanoplates (MnO@PEG-GMBP1 NPs) for monitoring of MDR gastric cancer through magnetic resonance imaging (MRI). The generated MnO@PEG-GMBP1 NPs had a size of about 11 nm and exhibited a good colloidal stability in PBS and in 10% FBS medium. Serial MRI studies in mice demonstrated that the magnetic resonance signal intensity, at the tumor site, reached a peak at 3 h after tail vein injection of MnO@PEG-GMBP1 NPs. The specific targeting ability of MDR gastric cancer cells (SGC7901/ADR) by MnO@PEG-GMBP1 NPs was authenticated , and by immunofluorescence analysis experiments. The systematic safety evaluation indicated that the toxicity of MnO@PEG-GMBP1 NPs in mice was negligible. Therefore, the GMBP1 conjugated MnO nanoplates can be clinically used for accurate imaging and monitoring of MDR gastric cancer.
多药耐药（MDR）是胃癌化疗面临的巨大挑战。因此，准确监测MDR对胃癌治疗具有重要意义。GMBP1是一种细胞外内化肽，可通过与GRP78特异性结合来靶向MDR胃癌细胞，GRP78是一种在胃癌细胞中过表达的MDR相关蛋白。在此，我们构建了GMBP1偶联的MnO纳米片（MnO@PEG-GMBP1 NPs），用于通过磁共振成像（MRI）监测MDR胃癌。所制备的MnO@PEG-GMBP1 NPs尺寸约为11 nm，在PBS和10%胎牛血清培养基中表现出良好的胶体稳定性。对小鼠进行的系列MRI研究表明，尾静脉注射MnO@PEG-GMBP1 NPs后3小时，肿瘤部位的磁共振信号强度达到峰值。通过免疫荧光分析实验验证了MnO@PEG-GMBP1 NPs对MDR胃癌细胞（SGC7901/ADR）的特异性靶向能力。系统安全性评估表明，MnO@PEG-GMBP1 NPs对小鼠的毒性可忽略不计。因此，GMBP1偶联的MnO纳米片可临床用于MDR胃癌的精确成像和监测。
