Noah J. J. Johnson

Self-focusing by Ostwald ripening: a strategy for layer-by-layer epitaxial growth on upconverting nanocrystals.

We demonstrate a novel epitaxial layer-by-layer growth on upconverting NaYF(4) nanocrystals (NCs) utilizing Ostwald ripening dynamics tunable both in thickness and composition. Injection of small sacrificial NCs (SNCs) as shell precursors into larger core NCs results in the rapid dissolution of the SNCs and their deposition onto the larger core NCs to yield core-shell structured NCs. Exploiting this NC size dependent dissolution/growth, the shell thickness can be controlled either by manipulating the number of SNCs injected or by successive injection of SNCs. In either of these approaches, the NCs self-focus from an initial bimodal distribution to a unimodal distribution (σ <5%) of core-shell NCs. The successive injection approach facilitates layer-by-layer epitaxial growth without the need for tedious multiple reactions for generating tunable shell thickness, and does not require any control over the injection rate of the SNCs, as is the case for shell growth by precursor injection.

NaDyF4 Nanoparticles as T2 Contrast Agents for Ultrahigh Field Magnetic Resonance Imaging.

A major limitation of the commonly used clinical MRI contrast agents (CAs) suitable at lower magnetic field strengths (<3.0 T) is their inefficiency at higher fields (>7 T), where next-generation MRI scanners are going. We present dysprosium nanoparticles (β-NaDyF4 NPs) as T2 CAs suitable at ultrahigh fields (9.4 T). These NPs effectively enhance T2 contrast at 9.4 T, which is 10-fold higher than the clinically used T2 CA (Resovist). Evaluation of the relaxivities at 3 and 9.4 T show that the T2 contrast enhances with an increase in NP size and field strength. Specifically, the transverse relaxivity (r2) values at 9.4 T were ∼64 times higher per NP (20.3 nm) and ∼6 times higher per Dy(3+) ion compared to that at 3 T, which is attributed to the Curie spin relaxation mechanism. These results and confirming phantom MR images demonstrate their effectiveness as T2 CAs in ultrahigh field MRIs.

An Effective Polymer Cross-Linking Strategy To Obtain Stable Dispersions of Upconverting NaYF4 Nanoparticles in Buffers and Biological Growth Media for Biolabeling Applications

Ligands on the nanoparticle surface provide steric stabilization, resulting in good dispersion stability. However, because of their highly dynamic nature, they can be replaced irreversibly in buffers and biological medium, leading to poor colloidal stability. To overcome this, we report a simple and effective cross-linking methodology to transfer oleate-stabilized upconverting NaYF(4) core/shell nanoparticles (UCNPs) from hydrophobic to aqueous phase, with long-term dispersion stability in buffers and biological medium. Amphiphilic poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with and without poly(ethylene glycol) (PEG) was used to intercalate with the surface oleates, enabling the transfer of the UCNPs to water. The PMAO units on the phase transferred UCNPs were then successfully cross-linked using bis(hexamethylene)triamine (BHMT). The primary advantage of cross-linking of PMAO by BHMT is that it improves the stability of the UCNPs in water, physiological saline buffers, and biological growth media and in a wide range of pH values when compared to un-cross-linked PMAO. The cross-linked PMAO-BHMT coated UCNPs were found to be stable in water for more than 2 months and in physiological saline buffers for weeks, substantiating the effectiveness of cross-linking in providing high dispersion stability. The PMAO-BHMT cross-linked UCNPs were extensively characterized using various techniques providing supporting evidence for the cross-linking process. These UCNPs were found to be stable in serum supplemented growth medium (37 °C) for more than 2 days. Utilizing this, we demonstrate the uptake of cross-linked UCNPs by LNCaP cells (human prostate cancer cell line), showing their utility as biolabels.

Direct Evidence for Coupled Surface and Concentration Quenching Dynamics in Lanthanide-Doped Nanocrystals

Luminescence quenching at high dopant concentrations generally limits the dopant concentration to less than 1-5 mol% in lanthanide-doped materials, and this remains a major obstacle in designing materials with enhanced efficiency/brightness. In this work, we provide direct evidence that the major quenching process at high dopant concentrations is the energy migration to the surface (i.e., surface quenching) as opposed to the common misconception of cross-relaxation between dopant ions. We show that after an inert epitaxial shell growth, erbium (Er3+) concentrations as high as 100 mol% in NaY(Er)F4/NaLuF4 core/shell nanocrystals enhance the emission intensity of both upconversion and downshifted luminescence across different excitation wavelengths (980, 800, and 658 nm), with negligible concentration quenching effects. Our results highlight the strong coupling of concentration and surface quenching effects in colloidal lanthanide-doped nanocrystals, and that inert epitaxial shell growth can overcome concentration quenching. These fundamental insights into the photophysical processes in heavily doped nanocrystals will give rise to enhanced properties not previously thought possible with compositions optimized in bulk.

Lanthanide-Based Heteroepitaxial Core–Shell Nanostructures: Compressive versus Tensile Strain Asymmetry

Heteroepitaxial core-shell nanostructures have been proven advantageous in a wide variety of applications, ranging from luminescence enhancement, band gap engineering, multimodal theranostics, to catalysis. However, precisely tailoring the epitaxial growth is challenging, and a general understanding of the parameters that impact epitaxial growth remains unclear. Here we demonstrate the critical role of the sign of the lattice mismatch of the shell relative to the core (compressed/tensile) in generating lanthanide-based core-shell structures, a parameter conventionally not considered in heteroepitaxial design. We took advantage of the very gradual contraction of lanthanide ions along the series to control precisely both the magnitude and the sign of lattice mismatch and investigated multiple sodium lanthanide fluoride (NaLnF4) core-shell heterostructures of variable composition and size. We discovered that the tensile strained shells adapt to the core crystallite shape (i.e., conformal) and lattice structure (i.e., coherent), while under identical magnitude of mismatch, the compressively strained shells are neither conformal nor coherent to the core. This striking asymmetry between the tensile and compressively strained epitaxial growth arises from the fundamental anharmonicity of the interatomic interactions between the attractive and repulsive pairs. From a broader perspective, our findings redefine the a priori design consideration and provide a fundamental insight on the necessity to include the sign of lattice mismatch and not just its magnitude in designing heteroepitaxial core-shell nanostructures.

Compact Micellization: A Strategy for Ultrahigh T1 Magnetic Resonance Contrast with Gadolinium-Based Nanocrystals

Paramagnetic gadolinium (Gd(3+))-based nanocrystals (NCs) with a large number of confined gadolinium ions can be expected to heavily enhance the longitudinal (T1) relaxation of water protons compared to clinical gadolinium complexes with only a single paramagnetic center. However, paramagnetic Gd(3+)-NCs reported to date show only a modest T1 relaxivity of ∼10 mM(-1) s(-1) per Gd(3+) at 1.5 T, only about 3-times higher than clinical Gd(3+) complexes. Here we demonstrate a strategy that achieves ultrahigh T1 relaxivity that is about 25-times higher than clinical Gd(3+) complexes by controlling the proximity of water protons to a paramagnetic NC surface. Using NaGdF4 NCs (∼3 nm) coated with PEG-ylated phospholipid (DSPE-PEG) micelles, we show that the distance of water protons to the NCs surface can be tuned by controlling the NC-micelle sizes. Increasing the ratio of DSPE-PEG to NCs during micellization decreases the size of NC-micelles, enhancing the proximity of water to the NC surface. Using this strategy, we have achieved compact NC-micelles (hydrodynamic diameter, HD ∼ 5 nm) with ultrahigh T1 relaxivity of ∼80 mM(-1) s(-1) per Gd(3+) at 1.41 T. The findings reported here demonstrate a nanostructured Gd(3+)-contrast agent (CA) that simultaneously achieves an ultrahigh T1 relaxivity approaching theoretical predictions, extremely compact size (HD < 5 nm), and a biocompatible surface. Our results show the hitherto unknown ultrahigh T1 relaxation enhancement of water protons in close proximity to a colloidal gadolinium-NC surface that is achievable by precise control of their surface structure.

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

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.

Enhanced UV upconversion emission using plasmonic nanocavities

Strongly enhanced upconversion emission is experimentally demonstrated from an ensemble of β-NaYF₄:Gd³⁺/Yb³⁺/Tm³⁺ @NaLuF₄ core-shell nanoparticles trapped in judiciously designed plasmonic nanocavities. Using cross-shape silver nanocavities, 170-fold enhancement is obtained at UV band around 345 nm.

Engineering upconversion emission spectra using plasmonic nanocavities

We show that the upconversion emission spectra of Tm³⁺ and Yb³⁺ codoped β-NaYF₄-NaYF₄ core-shell nanoparticles can be judiciously modified by means of plasmonic nanocavities. Our analysis indicates that more than a 30-fold increase in conversion efficiency to the UV spectral band can be expected by engineering the NIR absorption and the local density of states. The effect of the nanocavity on the resulting radiation patterns is discussed. Our results are exemplified in cylindrical cavity geometries.

Increased upconversion quantum yield in plasmonic structures

Upconversion processes have found widespread applications in drug delivery, bio-imaging and solar-cells. In this paper we present a theoretical model that analyzes the impact of a plasmonic shield structure on the quantum yield of upconversion nanoparticles. We use this model to assess the efficiency of NaYF4: Tm3+ Yb3+/NaYF4 core-shell nanoparticles when embedded in a polymer matrix and covered by a metallic can-like structure. We find that as a result of this specific plasmonic structure, the upconversion luminescence from NIR to UV can be increased by a factor of 30.