Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China.
Nanoscale. 2020 Feb 21;12(7):4473-4490. doi: 10.1039/c9nr04976b. Epub 2020 Feb 7.
Precise diagnosis and effective treatment are crucial to the prognosis of pancreatic ductal adenocarcinoma (PDAC). Magnetic iron oxide nanoparticles (IONPs) are superior magnetic resonance imaging (MRI) contrast agents, while antibodies are significant immunotherapy reagents. Herein, we firstly generated a novel nanocomposite combining triple single chain antibodies (scAbs) and IONPs for the detection and treatment of PDAC.
Triple scAbs (scAbMUC4, scAbCEACAM6, scFvCD44v6, MCC triple scAbs) were conjugated to the surface of polyethylene glycol modified IONPs (IONPs-PEG), forming the IONPs-PEG-MCC triple scAbs nanocomposite. Characterization of the nanocomposite was performed, and its cytotoxicity, specificity, and apoptosis induction were evaluated. In vivo MRI study and anti-pancreatic cancer effect assessment were performed in tumor-bearing nude mice.
The size of the IONPs-PEG-MCC triple scAbs nanocomposite was about 23.6 nm. The nanocomposite was non-toxic to normal pancreatic ductal epithelial cells, and could specifically bind to and be internalized by MUC4/CEACAM6/CD44v6-expressing PDAC cells. With an r2 relaxivity of 104.2 mM s, the IONPs-PEG-MCC triple scAbs nanocomposite could significantly shorten the MRI T2-weighted signal intensity both in vitro and in vivo. The IONPs-PEG-MCC triple scAbs nanocomposite also showed a favorable anti-pancreatic cancer effect.
In the present study, the IONPs-PEG-MCC triple scAbs nanocomposite was firstly confirmed as a bi-functional nanocomposite in both MRI and treatment, providing its critical clinical transformation potential in PDAC detection and treatment.
精确诊断和有效治疗对胰腺导管腺癌（PDAC）的预后至关重要。磁性氧化铁纳米粒子（IONPs）是优越的磁共振成像（MRI）造影剂，而抗体是重要的免疫治疗试剂。在此，我们首次生成了一种新型纳米复合物，将三重单链抗体（scAbs）与 IONPs 结合，用于 PDAC 的检测和治疗。
三重 scAbs（scAbMUC4、scAbCEACAM6、scFvCD44v6、MCC 三重 scAbs）与聚乙二醇修饰的 IONPs（IONPs-PEG）表面缀合，形成 IONPs-PEG-MCC 三重 scAbs 纳米复合物。对纳米复合物进行了表征，并评估了其细胞毒性、特异性和凋亡诱导作用。在荷瘤裸鼠中进行了体内 MRI 研究和抗胰腺癌作用评估。
IONPs-PEG-MCC 三重 scAbs 纳米复合物的大小约为 23.6nm。该纳米复合物对正常胰腺导管上皮细胞无毒性，可特异性结合并被 MUC4/CEACAM6/CD44v6 表达的 PDAC 细胞内化。其 r2 弛豫率为 104.2mM·s，该 IONPs-PEG-MCC 三重 scAbs 纳米复合物在体外和体内均能显著缩短 MRI T2 加权信号强度。IONPs-PEG-MCC 三重 scAbs 纳米复合物还显示出良好的抗胰腺癌作用。
在本研究中，IONPs-PEG-MCC 三重 scAbs 纳米复合物首次被确认为 MRI 和治疗的双功能纳米复合物，为其在 PDAC 检测和治疗中的关键临床转化潜力提供了依据。
