Simultaneous Enhancement of Photoluminescence, MRI Relaxivity, and CT Contrast by Tuning the Interfacial Layer of Lanthanide Heteroepitaxial Nanoparticles

Abstract

Nanoparticle (NP) based exogenous contrast agents assist biomedical imaging by enhancing the target visibility against the background. However, it is challenging to design a single type of contrast agents that are simultaneously suitable for various imaging modalities. The simple integration of different components into a single NP contrast agent does not guarantee the optimized properties of each individual components. Herein, we describe lanthanide-based core–shell–shell (CSS) NPs as triple-modal contrast agents that have concurrently enhanced performance compared to their individual components in photoluminescence (PL) imaging, magnetic resonance imaging (MRI), and computed tomography (CT). The key to simultaneous enhancement of PL intensity, MRI r1 relaxivity, and X-ray attenuation capability in CT is tuning the interfacial layer in the CSS NP architecture. By increasing the thickness of the interfacial layer, we show that (i) PL intensity is enhanced from completely quenched/dark state to brightly emissive state of both upconversion and downshifting luminescence at different excitation wavelengths (980 and 808 nm), (ii) MRI r1 relaxivity is enhanced by 5-fold from 11.4 to 52.9 mM−1 s−1 (per Gd3+) at clinically relevant field strength 1.5 T, and (iii) the CT Hounsfield Unit gain is 70% higher than the conventional iodine-based agents at the same mass concentration. Our results demonstrate that judiciously designed contrast agents for multimodal imaging can achieve simultaneously enhanced performance compared to their individual stand-alone structures and highlight that multimodality can be achieved without compromising on individual modality performance.

Advances in highly doped upconversion nanoparticles

“…Blocking layer separation: In addition to the strategies of tuning excitation and emission properties, the control over doping location with a blocking layer (Figure 3e ) has been demonstrated for orthogonal emissions 78 , 80 , 81 , spectral/lifetime multiplexing 82 , upconverting/downshifting 83 , multimode imaging 84 , and multi-optical functions in single particles 65 . For example, reversible isomerization of spiropyran derivatives has been achieved by the orthogonal emissions of core@multishell UCNPs with a high-doping concentration of Nd 3+ under irradiation at 800 and 980 nm (Figure 3f ) 80 .…”

Excretable Lanthanide Nanoparticle for Biomedical Imaging and Surgical Navigation in the Second Near‐Infrared Window

“…Thus, it has emerged as the next-generation imaging technique for in vivo biomedical imaging. [23][24][25][26][27][28][29][30][31] Nevertheless, like most of reported NIR-II inorganic nanoparticles, long retention in reticuloendothelial system (RES) and inability to clear from living body lead to the existing dilemmas in the RENPs, which also raise the potential safety concerns and greatly hamper their future broad biomedical applications and translation. [20][21][22][23][24] However, tedious synthetic procedure and low quantum yield of organic molecules are still the main chemical impediments that make them lie behind the inorganic counterparts.…”

Surface Engineering to Boost the Performance of Nanoparticle‐Based T1 Contrast Agents

“…(d) Comparison of surface area with Gd 3+ per particle and tumbling time of small α‐NaGdF 4 NPs and β‐NaYb/ErF 4 @NaLuF4@NaGdF 4 nanocomposites. Reproduced from ref . Copyright (2017), with permission from the American Chemical Society.…”