451870 The Design of Micelles for Molecular Diagnostics
Specifically, CREKA micelles consisting of DSPE-PEG2000-DTPA(Gd) were spherical and approximately 10 nm confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). CREKA micelles incorporating either DSPE-DTPA(Gd) or BSA-DTPA(Gd) formed a mixed populations of spherical and cylindrical nanoparticles. Upon addition to fibrin clots in vitro, CREKA micelles with DSPE-PEG2000-DTPA(Gd) showed statistically significant binding capabilities compared to its non-targeting counterpart (no peptide). In comparison, CREKA micelles with DSPE-DTPA(Gd) or BSA-DTPA(Gd) showed no difference compared to its non-targeting counterparts. From these results, CREKA micelles incorporating DSPE-PEG2000-DTPA(Gd), or CREKA-Gd micelles, were used for further studies. T1 values decreased with increasing Gd content (2278-897 ms for 100% DSPE-PEG2000-CREKA micelles-25/75% DSPE-PEG2000-CREKA/DSPE-PEG2000-DTPA(Gd)) confirming efficacy as contrast agents. Upon injecting into late-stage atherosclerotic mice, enhanced signal was found at the aortic arch via MRI by both types of micelles, further confirmed via ex vivo fluorescence imaging. Clearance of micelles was found to be mainly through the liver and spleen, or the reticuloendothelial system, and H and E results of organ sections showed no morphological abnormalities.
In sum, novel nanoparticles for MRI were designed using various gadolinium chelators. Our data supports the importance of molecular design of self-assembling particles as it relates to functional and biological efficacy for disease diagnostics. Future studies will incorporate therapeutic components and dual MRI/positron electron tomography capabilities to enhance signal sensitivity.