Brian Yust

Stokes emission in GdF3:Nd3+ nanoparticles for bioimaging probes

There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to their sharp absorption and photoluminescence (PL) in the near infrared (NIR) spectral region. These NIR based nanoparticles (NPs) could allow biological imaging at substantial depths with enhanced contrast and high spatial resolution due to the absence of auto fluorescence in biological samples under infrared excitation. Here, we present the highly efficient infrared photoluminescence in GdF₃:Nd(3+) nanoparticles under 800 nm excitation within the hydrodynamic size limitations for bio-applications. The downconversion (Stokes emission) absolute quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion (Stokes emission) QYs of approximately 5 ± 2 nm sized GdF₃:1% Nd(3+) colloidal NPs are 2000 times higher than those of efficient upconversion (UC) particles NaYF₄:20% Er/2% Yb of the same size. Furthermore, the utility of these NIR emitting nanoparticles for bioimaging probes has been demonstrated by confocal imaging and spectroscopic study.

Enhancement of nonlinear optical properties of BaTiO3 nanoparticles by the addition of silver seeds.

Barium titanate (BaTiO3) is a technologically important material because of its nonlinear properties, such as its strong second harmonic generation and high third order susceptibility. While many nonlinear effects have been extensively studied on the bulk scale, there are still questions regarding the strength of nonlinear effects in nanoparticles. The nonlinear properties of BaTiO3 nanoparticles and nanorods have been studied using the closed aperture z-scan technique. Silver was then grown photochemically on the surface of the BaTiO3 nanoparticles, and it was found that the third order susceptibility increases dramatically.

Interphotoreceptor Retinoid‐Binding Protein Protects Retinoids from Photodegradation

Retinol degrades rapidly in light into a variety of photoproducts. It is remarkable that visual cycle retinoids can evade photodegradation as they are exchanged between the photoreceptors, retinal pigment epithelium and Müller glia. Within the interphotoreceptor matrix, all‐trans retinol, 11‐cis retinol and retinal are bound by interphotoreceptor retinoid‐binding protein (IRBP). Apart from its role in retinoid trafficking and targeting, could IRBP have a photoprotective function? HPLC was used to evaluate the ability of IRBP to protect all‐trans and 11‐cis retinols from photodegradation when exposed to incandescent light (0 to 8842 μW cm−2); time periods of 0–60 min, and bIRBP: retinol molar ratios of 1:1 to 1:5. bIRBP afforded a significant prevention of both all‐trans and 11‐cis retinol to rapid photodegradation. The effect was significant over the entire light intensity range tested, and extended to the bIRBP: retinol ratio 1:5. In view of the continual exposure of the retina to light, and the high oxidative stress in the outer retina, our results suggest IRBP may have an important protective role in the visual cycle by reducing photodegradation of all‐trans and 11‐cis retinols. This role of IRBP is particularly relevant in the high flux conditions of the cone visual cycle.

Ultrasmall lanthanide-doped nanoparticles as multimodal platforms

Recently, there has been a great amount of interest in nanoparticles which are able to provide a platform with high contrast for multiple imaging modalities in order to advance the tools available to biomedical researchers and physicians. However, many nanoparticles do not have ideal properties to provide high contrast in different imaging modes. In order to address this, ultrasmall lanthanide doped oxide and fluoride nanoparticles with strong NIR to NIR upconversion fluorescence and a strong magnetic response for magnetic resonance imaging (MRI) have been developed. Specifically, these nanoparticles incorporate gadolinium, dysprosium, or a combination of both into the nano-crystalline host to achieve the magnetic properties. Thulium, erbium, and neodymium codopants provide the strong NIR absorption and emission lines that allow for deeper tissue imaging since near infrared light is not strongly absorbed or scattered by most tissues within this region. This also leads to better image quality and lower necessary excitation intensities. As a part of the one pot synthesis, these nanoparticles are coated with peg, pmao, or d-glucuronic acid to make them water soluble, biocompatible, and bioconjugable due to the available carboxyl or amine groups. Here, the synthesis, morphological characterization, magnetic response, NIR emission, and the quantum yield will be discussed. Cytotoxicity tested through cell viability at varying concentrations of nanoparticles in growth media will also be discussed.

Rare Earth doped nanoparticles in imaging and PDT

Nanoparticles doped with rare earth ions for biomedical imaging and infrared photodynamic therapy (IRPDT) have been synthesized, characterized, and compared. Specifically, these nanoparticles utilize two primary modalities: near infrared excitation and emission for imaging, and near infrared upconversion for photodynamic therapy. These nanoparticles are optimized for both their infrared emission and upconversion energy transfer to a photoactive agent conjugated to the surface. Finally, these nanoparticles are tested for toxicity, imaged in cells using the near infrared emission pathway, and used for selective killing of cells through the upconversion driven IRPDT.

Effect of Silver Coating on Barium Titanium Oxide Nanoparticle Toxicity.

Nanoparticles are presently being studied for optical and biomedical applications such as medical imaging and drug delivery. Nanoparticles impact the cellular environment due to many variables such as size, shape, and composition. How these factors affect cell viability is not fully understood. The purpose of this study is to test the toxicity effects of silver coating (Ag@) Barium Titanium Oxide (BaTiO3) nanoparticles on Rhesus Monkey Retinal Endothelial cells (RhRECs) in culture. The addition of silver to the nanoparticles increases their nonlinear optical properties significantly, making the Ag@BaTiO3 nanoparticles good candidates for nonlinear microscopy contrast agents. We hypothesize that by silver coating nanoparticles, there will be an increase in cell viability at higher concentrations when compared to non-silver coated nanoparticles. RhRECs were treated with BaTiO3 and Ag@BaTiO3 at concentrations of 0, 1.0, 10.0, and 100μg/ml for 24 hours at 370C + 5%CO2. After 24 hour incubation with respective nanoparticles, cell viability was determined using the trypan blue dye-exclusion method. Treatment with 0, 1.0 and 10.0μg/ml of Ag@BaTiO3 had minimal effect on cell viability, with 90% viable cells remaining at the end of the 24 hours treatment period. However, cells treated with 100μg/ml of Ag@BaTiO3 resulted in a decrease to 51% viable cells. Comparatively, cells treated with 0, 1.0 and 10μg/ml of BaTiO3 had no significant effect on cell viability (90% viable cells after treatment) while the 100μg/ml treatment resulted in a decrease to 29% viable cells. These results show that silver coating of BaTiO3 nanoparticles has a protective effect on cellular toxicity at high concentrations.

Phase conjugating nanomirrors: utilizing optical phase conjugation for imaging

Barium titanate (BaTiO3) is a good candidate for phase conjugation on the nano-scale, as four-wave mixing has been shown in nanoparticles of this type. Also, the ability to dope this material with rare earth elements, with strong absorption and emission lines, makes it possible to use these as multi-functional, multi-modal probes for biomedical applications. BaTiO3 nanoparticles are synthesized using a precipitation method and fully characterized. These particles are used in a four wave mixing setup to optically conjugate scattered light traveling through turbid media, such as tissue, to re-obtain lost image information due to the scattering process.

A comparison of methods for determining optical properties of thin samples

The near-infrared (NIR) optical properties of human retinal pigmented epithelial (RPE) cells and rare earth nanopowders were studied using a double-integrating sphere setup. The Kubelka-Munk and Inverse Adding-Doubling techniques were applied to obtain absorption and scattering coefficients. These are compared with the coefficients obtained through the Representative Layer Theory described by the Dahm equation. Retinal pigmented epithelial monolayers were cultured from an ARPE19 line in thin cell culture windows, and the nanopowders were pressed into samples of varying thickness. Samples were optically characterized as a function of wavelength. A brief discussion of the shortcomings of existing techniques for computing optical properties when applied to physically thin samples is provided, followed by a comparison between the optical properties of the samples returned by the different techniques.

Effect of surface coating of KYb2F7:Tm3+ on optical properties and biomedical applications

This project aims to provide an insight on the effects of biocompatible polymers on the optical properties and the nanoparticle-cell interaction of KYb2F7:Tm(3+) nanocrystals that exhibit strong near infrared (NIR) fluorescence. KYb2F7:Tm(3+) nanocrystals were synthesized with a diameter of 20-30 nm and surface modified with poly(ethylene glycol), Pluronic(®) F-127, and poly(N-vinylpyrrolidone), due to the associated advantages. Some of these include biocompatibility and biodistribution in the instance of agglomeration and hydrophobicity as well as the addition of a targeting agent and drug loading by further functionalization. Despite the decrease in fluorescence intensity induced by the surface modification, thuliums emission fingerprint was easily detected. Moreover, surface modified KYb2F7:Tm(3+) nanocrystals failed to induce a toxic response on endothelial cells following a 24 h uptake period up to concentrations of 100 μg ml(-1). In vitro toxicity and confocal imaging have demonstrated the versatility of these NIR fluorescence nanocrystals in biomedical imaging, drug delivery, and photodynamic therapy.

Effects of surface chemistry on the optical properties and cellular interaction of lanthanide-based nanoparticles

Fluorescent nanoparticles (NPs) such as KYb2F7:Tm3+ potential in biomedical applications due to their ability to absorb and emit within the biological window, where near infrared light is less attenuated by soft tissue. This results in less tissue damage and deeper tissue penetration making it a viable candidate in biological imaging. Another big factor in determining their ability to perform in a biological setting is the surface chemistry. Biocompatible coatings, including polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), pluronic and folic acid are commonly used because they pose several advantages such as ease of functionalization, better dispersion, and higher cellular uptake. To study the effects of the NP surface chemistry, KYb2F7:Tm3+ a solvothermal method using PEG, PVP, pluronic acid, and folic acid as a capping agent, followed by thorough optical characterizations. Optical changes were thoroughly studied and compared using absorption, emission, and quantum yield data. Cell viability was obtained by treating Rhesus Monkey Retinal Endothelial cells (RhREC) with KYb2F7:Tm3+ and counting viable cells following a 24 hour uptake period. The work presented will compare the optical properties and toxicity dependency on the surface chemistry on KYb2F7:Tm3+. The results will also indicate that KYb2F7:Tm3+ nanoparticles are viable candidates for various biomedical applications.