Gd3+-Functionalized Lithium Niobate Nanoparticles for Dual Multiphoton and Magnetic Resonance Bioimaging

Harmonic nanoparticles (HNPs) have emerged as appealing exogenous probes for optical bioimaging due to their distinctive features such as long-term photostability and spectral flexibility, allowing multiphoton excitation in the classical (NIR-I) and extended near-infrared spectral windows (NIR-II and -III). However, like all other optical labels, HNPs are not suitable for whole-body imaging applications. In this work, we developed a bimodal nonlinear optical/magnetic resonance imaging (MRI) contrast agent through the covalent conjugation of Gd(III) chelates to coated lithium niobate HNPs. We show that the resulting nanoconjugates exert strong contrast both in T1-weighted MRI of agarose gel-based phantoms and in cancer cells by harmonic generation upon excitation in the NIR region. Their capabilities for dual T1/T2 MRI were also emphasized by the quantitative mapping of the phantom in both modes. The functionalization protocol ensured high stability of the Gd-functionalized HNPs in a physiological environment and provided a high r1 relaxivity value per NP (5.20 × 105 mM–1 s–1) while preserving their efficient nonlinear optical response.