Nanoparticles modified by triple single chain antibodies for MRI examination and targeted therapy in pancreatic cancer
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, meanwhile antibodies are significant immunotherapy reagent. 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, cytotoxicity, specificity, and apoptosis induction of the nanocomposite were evaluated. In vivo MRI study and anti-pancreatic cancer effect assessment were performed through tumor-bearing nude mice. Results: The size of IONPs-PEG-MCC triple scAbs 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 a r2 relaxivity of 104.2 mM−1 s−1, IONPs-PEG-MCC triple scAbs could significantly shorten MRI T2-weighted signal intensity both in vitro and in vivo. IONPs-PEG-MCC triple scAbs also showed favorable anti-pancreatic cancer effect. Conclusion: In present study, IONPs-PEG-MCC triple scAbs was firstly confirmed as a bi-functional nanocomposite in both MRI and treatment, providing its critical clinical transformation potential in PDAC detection and treatment.