Target-Specific Magnetic Resonance Imaging of Human Prostate Adenocarcinoma Using NaDyF<sub>4</sub>–NaGdF<sub>4</sub> Core–Shell Nanoparticles
Armita Dash, Barbara Błasiak, Bogusław Tomanek, Peter Latta, Frank C. J. M. van Veggel
Abstract
We illustrate the development of NaDyF4–NaGdF4 core–shell nanoparticles (NPs) for targeting prostate cancer cells using a preclinical 9.4 T magnetic resonance imaging (MRI) of live animals. The NPs composed of paramagnetic Dy3+ and Gd3+ (T2- and T1-contrast agents, respectively) demonstrate proton relaxivities of r1 = 20.2 mM–1 s–1 and r2 = 32.3 mM–1 s–1 at clinical 3 T and r1 = 9.4 mM–1 s–1 and r2 = 144.7 mM–1 s–1 at preclinical 9.4 T. The corresponding relaxivity values per NP are r1 = 19.4 × 105 mMNP–1 s–1 and r2 = 33.0 × 105 mMNP–1 s–1 at 3 T and r1 = 9.0 × 105 mMNP–1 s–1 and r2 = 147.0 × 105 mMNP–1 s–1 at 9.4 T. In vivo active targeting of human prostate tumors grown in nude mice revealed docking of anti-prostate-specific membrane antigen (PSMA) antibody-tagged NPs at tumor sites post-24 h of their intravenous injection. On the other hand, in vivo passive targeting showed preferential accumulation of NPs at tumor sites only within 2 h of their injection, ascribed to the enhanced permeation and retention effect of the tumor. A biodistribution study employing the harvested organs of mice, post-24 h injection of NPs, quantified active targeting as nearly twice as efficient as passive targeting. These outcomes provide potential opportunities for noninvasive diagnosis using NaDyF4–NaGdF4 core–shell NPs for target-specific MRI.