Lanthanide-Based Heteroepitaxial Core–Shell Nanostructures: Compressive <i>versus</i> 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>i.e.</i>, conformal) and lattice structure (<i>i.e.</i>, 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 <i>a priori</i> 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 (Gd³⁺)-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 Gd³⁺-NCs reported to date show only a modest T₁ relaxivity of ∼10 mM^–1 s^–1 per Gd³⁺ at 1.5 T, only about 3-times higher than clinical Gd³⁺ complexes. Here we demonstrate a strategy that achieves ultrahigh T₁ relaxivity that is about 25-times higher than clinical Gd³⁺ 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 Gd³⁺ at 1.41 T. The findings reported here demonstrate a nanostructured Gd³⁺-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

Long-Term Colloidal Stability and Photoluminescence Retention of Lead-Based Quantum Dots in Saline Buffers and Biological Media through Surface Modification

Lead-based quantum dots (QDs) can be tuned to emit in the transparent region of the biological tissue (700 to 1100 nm) which make them a potential candidate for optical bioimaging. However, to employ these QDs as biolabels they have to retain their luminescence and maintain their colloidal stability in water, physiological saline buffers, different pH values, and biological media. To achieve this, four different surface modification strategies were tried: (1) silica coating; (2) ligand exchange with polyvinylpyrrolidone; (3) polyethyleneglycol-oleate (PEG-oleate) intercalation into the oleate ligands on the surface of the QDs; and (4) intercalation of poly­(maleicanhydride-<i>alt</i>-1-octadecene) (PMAO) into the oleate ligands on the surface of the QDs and further cross-linking of the PMAO. The first two methods exhibited excellent dispersion stability in water, but did not retain their photoluminescence. On the other hand, the intercalation strategy with PEG-oleate helped the QDs retain their luminescence but with poor colloidal stability in water. The fourth and final strategy involving intercalation and cross-linking of the amphiphilic polymer PMAO provided the QDs with colloidal stability in water but also resulted in the QDs retaining their luminescence as well. This process involved two steps; (1) the intercalation between octadecene chains of PMAO with the oleates on the surface of the QDs with some of the anhydride rings opened with PEG-amine; (2) the anhydride rings were cross-linked with bis­(hexamethylene)­triamine (BHMT) to avoid detachment of the polymer from the surface of QDs because of the polymer’s dynamic nature in solvents. The presence of PEG molecules potentially improves the biocompatibility of the QDs and the presence of carboxylic acids after reaction with BHMT makes them suitable for further surface functionalization with antibodies, proteins, and so forth. The surface-modified QDs have excellent dispersibility in water, saline buffers, and in various pH conditions for more than 7 months and more than 20 days in serum-supplemented growth media. In addition to the colloidal stability, the QDs retained their photoluminescence even after 7 months in the aforementioned aqueous media. The intercalation and cross-linking process have also made the QDs resistant to oxidation when exposed to ambient atmosphere and aqueous media

Leveraging Spectral Matching between Photosensitizers and Upconversion Nanoparticles for 808 nm-Activated Photodynamic Therapy

Upconversion nanoparticles (UCNPs) are promising platforms to enhance the therapeutic response of cancer cells toward photodynamic therapy (PDT). When coupled with UCNPs, the photosensitizers in PDT are indirectly activated by near-infrared (NIR) excitation that allows for deeper tissue penetration and reduced attenuation. To achieve maximum performance, the upconverted emission peak of the UCNPs and absorption band of the photosensitizers need to overlap significantly. However, the spectral mismatch between the upconverted emission maximum of UCNPs (predominantly in the green) and absorption maximum of most available photosensitizers (in the red) greatly limits the therapeutic efficacy of current UCNP-PDT platforms. Here we report a UCNP-PDT platform that under biobenign 808 nm NIR excitation shows a strong spectral overlap between the UCNP emission (λ_em) and absorption of zinc phthalocyanine photosensitizers (λ_abs). The spectrally matched UCNP red emission band is 40 times stronger than the green emission band and is independent of laser excitation power across a wide range (0.6–3.4 W/cm²) applicable in biological systems. The spectrally matched UCNP-PDT platform enables rapid generation (5 min) of cytotoxic singlet oxygen via near-infrared excitation at extremely low laser power density of only 0.6 W/cm². Finally, we show that the actively growing HeLa cancer cell spheroids with 3 mm diameter can be effectively suppressed with 65% drop of the cell viability, demonstrating the suitability and effectiveness of the spectrally matched UCNP-PDT platforms for cancer therapeutics

Local Structure of Rare-Earth Fluorides in Bulk and Core/Shell Nanocrystalline Materials

NaREF₄ (rare-earth, RE = Y, Lu) nanocrystals (NCs) containing Ln³⁺-dopants are of great interest due to their unique ability to downshift, downconvert, and upconvert light. While the luminescent properties and microscale structures of such NCs are well understood, relatively little is known about their molecular-level structures, the nature of the NC cores and shells, and the interactions of the stabilizing ligands at the NC surface. To address these issues, we present a comprehensive characterization of bulk β-NaYF₄, one of the most commonly used hosts for Ln³⁺-dopants in luminescent NCs. Using a combination of powder X-ray diffraction (pXRD) and multinuclear (⁸⁹Y, ²³Na, ¹⁹F) solid-state nuclear magnetic resonance (SSNMR) spectroscopy, we provide conclusive evidence that this compound crystallizes in a hexagonal <i>P</i>6₃/<i>m</i> structure, resolving a longstanding debate. The structure of this bulk form is related to the structure of NaYF₄/NaLuF₄ core/shell NCs. From the similarities between the ¹⁹F and ²³Na SSNMR spectra of the bulk and NC materials, it is concluded that the NCs have the same β-NaYF₄ and β-NaLuF₄ phases as the bulk compounds. A series of cross-polarization NMR experiments confirm the presence of oleates on the surface of the particle via their proximity to surface Na⁺ sites

Probing the Structure of NaYF₄ Nanocrystals using Synchrotron-Based Energy-Dependent X‑ray Photoelectron Spectroscopy

Understanding the structure and chemical speciation of the synthesized lanthanide-doped NaYF₄ nanocrystals is of paramount importance to improve and optimize their physical and chemical properties. Hence in this work we employ synchrotron-based high-resolution X-ray photoelectron spectroscopy (XPS) measurements to analyze lanthanide-doped and undoped NaYF₄ nanocrystals. These measurements revealed that there are two doublets for the yttrium ions in the nanocrystal instead of the single doublet in case all Y³⁺ ions have the same chemical environment, generally observed around a binding energy of 160 eV (3d photoelectrons of Y³⁺). This second doublet (binding energy ∼ 157.5 eV) was convoluted with the first doublet (binding energy ∼ 160 eV), and the intensity of this doublet increased with a decrease in excitation X-ray energy. The second doublet was confirmed to belong to the yttrium ions as doped and undoped NaYF₄ nanocrystals exhibit this second peak. The peaks were deconvoluted showing that the second peak is also a doublet with the ratio of the peaks being 2:3. This is exactly the same as what we have observed for the first doublet of the 3d photoelectrons of yttrium ions. In addition, we observe an increase in intensity of the second doublet in comparison to the original 3d doublet of the yttrium ions as the excitation energy is decreased. This suggests that the second doublet is from surface yttrium ions in the NaYF₄ nanocrystal. To confirm our hypothesis, a shell of NaYbF₄ or NaTmF₄ was grown over the NaYF₄ nanocrystal and the second doublet for the yttrium ions was not observed. This is an additional confirmation that the second doublet is indeed from the surface yttrium ions. This implies that the yttriums on the surface of the nanocrystals have a (slightly) different chemical speciation than their counterparts inside the nanocrystals. We attribute the new chemical speciation of surface yttrium ions to the different chemical environment they encounter than their counterparts inside the nanocrystal

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 NaYF₄ core/shell nanoparticles (UCNPs) from hydrophobic to aqueous phase, with long-term dispersion stability in buffers and biological medium. Amphiphilic poly­(maleic anhydride-<i>alt</i>-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

Accurate Coulometric Quantification of Hydrogen Absorption in Palladium Nanoparticles and Thin Films

We report here an electrochemical method for precise and accurate quantification of hydrogen absorption in palladium materials. We demonstrate that conventional chronocoulometry over-reports adsorbed hydrogen due to charge from the accompanying hydrogen oxidation reaction (HOR). We designed and built a bespoke electrochemical flow cell that mitigates the concurrent HOR reaction and consequently provides improved accuracy and reproducibility relative to other existing electrochemical techniques. The efficacy of this technique is demonstrated experimentally for a series of palladium sample types: a 100 nm electron-beam deposited thin film, a 20 μm electrodeposited palladium film, a casting of 21 nm edge-length cubic nanoparticles, and a casting of 27 nm edge-length octahedral nanoparticles. We contend that this method is the most effective for measuring hydrogen uptake in different palladium samples

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 <i>T</i>₂ 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 <i>T</i>₂ contrast enhances with an increase in NP size and field strength. Specifically, the transverse relaxivity (<i>r</i>₂) values at 9.4 T were ∼64 times higher per NP (20.3 nm) and ∼6 times higher per Dy³⁺ 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

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 <i>r</i>₁ 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 <i>r</i>₁ 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