Nanoparticles modified by triple single chain antibodies for MRI examination and targeted therapy in pancreatic cancer
Jinmao Zou, Shangxiang Chen, Yaqing Li, Linjuan Zeng, Guoda Lian, Jiajia Li, Shaojie Chen, Kaihong Huang, Yinting Chen
Abstract
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. METHODS: 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. RESULTS: , 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. CONCLUSION: 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.