Gd3+-ion-doped upconversion nanoparticles (UCNPs), integrating the advantages of upconversion luminescence and magnetic resonance imaging (MRI) modalities, are capturing increasing attention because they are promising to improve the accuracy of diagnosis. The embedded Gd3+ ions in UCNPs, however, have an indistinct MRI enhancement owing to the inefficient exchange of magnetic fields with the surrounding water protons. In this study, a novel approach is developed to improve the MR imaging sensitivity of Gd3+-ion-doped UCNPs. Bovine serum albumin (BSA) bundled with DTPA-Gd3+ (DTPAGd) is synthesized both as the MR imaging sensitivity synergist and phase-transfer ligand for the surface engineering of UCNPs. The external Gd3+ ion attachment strategy is found to significant improve the MR imaging sensitivity of Gd3+-ion-doped UCNPs. The relaxivity analysis shows that UCNPs@BSA·DTPAGd exhibit higher relaxivity values than do UCNPs@BSA without DTPAGd moieties. Another relaxivity study discloses a striking message that the relaxivity value does not always reflect the realistic MRI enhancement capability. The high concentration of Gd3+-ion-containing UCNPs with further surface-engineered BSA·DTPAGd (denoted as UCNPs–H@BSA·DTPAGd) exhibits a more pronounced MRI enhancement capability compared to the other two counterparts [UCNPs–N@BSA·DTPAGd and UCNPs–L@BSA·DTPAGd (−N and –L are denoted as zero and low concentrations of Gd3+ ion doping, respectively)], even though it holds the lowest r1 of 1.56 s–1 per mmol L–1 of Gd3+. The physicochemical properties of UCNPs are essentially maintained after BSA·DTPAGd surface decoration with good colloidal stability, in addition to improving the MR imaging sensitivity. In vivo T1-weighted MRI shows potent tumor-enhanced MRI with UCNPs–H@BSA·DTPAGd. An in vivo biodistribution study indicates that it is gradually excreted from the body via hepatobiliary and renal processing with no obvious toxicity. It could therefore be concluded, with improved MR imaging sensitivity by an internal and external incorporation of Gd3+ strategy, that UCNPs–H@BSA·DTPAGd presents great potential as an alternative in tumor-targeted MR imaging.
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 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−1 s−1, 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.
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