Parul Rungta

Selective Imaging and Killing of Cancer Cells with Protein-Activated Near-Infrared Fluorescing Nanoparticles

We present a general approach for the selective imaging and killing of cancer cells using protein-activated near-infrared emitting and cytotoxic oxygen generating nanoparticles. Poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of azide-terminated indocyanine green (azICG), a near-infrared emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic ninefold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response. Human liver carcinoma cells (HepG2) overexpress albumin proteins and could be employed to activate the fluorescence of the nanoparticles. Preliminary PDT studies with HepG2 cells combined with the modified particles indicated that a minor exposure of 780 nm radiation resulted in a statistically significant reduction in cell growth.

Designing fluoroprobes through Förster resonance energy transfer: surface modification of nanoparticles through “click” chemistry

Aqueous-phase 83 nm poly(propargyl acrylate) (PA) nanoparticles were surface-functionalized with sparingly water soluble fluorescent moieties through a copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) (i.e., “click” transformation) to produce fluoroprobes with a large Stokes shift. For moieties which could not achieve extensive surface coverage on the particles utilizing a standard click transformation procedure, the presence of β-cyclodextrin (β-CD) during the transformation enhanced the grafting density onto the particles. Moieties containing oxadiazolyl groups exhibited an 84% increase in grafting density when the transformation was performed in the presence of the oligosaccharide, going from 1.04 oxadiazolyl groups/nm2 to 1.91 oxadiazolyl groups/nm2. Similarly, an azide-modified coumarin 6 (AD1) underwent a 17% enhancement in grafting density from 1.56 AD1 groups/nm2 to 1.82 AD1 groups/nm2 when the transformation was done in the presence of β-CD. A polyethylene glycol modified naphthalimide-based emitter (AD2) was less sensitive to the presence of β-CD due to its elevated water solubility and exhibited a 5% increase in grafting density. In contrast, a carbazolyl-containing moiety which could achieve 100% surface coverage of the particles without the use of β-CD exhibited a slight retardation in the incorporation rate (and final grafting density) onto the particle when the oligosaccharide was employed. Photoluminescence studies of the particles modified singly or with multiple moieties indicated that when oxadiazolyl and carbazolyl groups were attached to the particles, an exciplex was formed that had a peak emission at ca. 400 nm. The absorption of the surface attached naphthalimide-based dye exhibited a complete spectral overlap with the carbazole/oxadiazole exciplex emission and photoluminescence excitation studies indicated an efficient energy transfer process from the carbazolyl and oxadiazolyl groups to the dye, resulting in an emission maxima at 510 nm for the modified particles and a total Stokes shift of 180 nm. This large Stokes shift is an important determinant of the ultimate sensitivity of a fluoroprobe, where scattering and background fluorescence can interfere with the detection of low concentrations of an analyte and the ability to manipulate the separation between the excitation and emission wavelengths is a critical parameter for optimal detection.

Colloidal templating: seeded emulsion polymerization of a soluble shell with a controlled alkyne surface density

A general methodology for producing ca. 100 nm core–shell colloidal particles in which the shell has an elevated alkyne functionality and yet remains thermoplastic is presented. The availability of accessible alkyne groups on the surface of the aqueous-phase particles allows for the in situ surface modification of the particles through a copper(I) catalyzed Huisgen 1,3-dipolar cycloaddition with an azide-terminated surface agent. The core is an extensively crosslinked polymer which can be easily removed by dispersing the particles in a solvent and centrifuging and collecting the cores, leaving the solubilized shells. This allows for the complete characterization of the colloidal surface reactions in the absence of the volumetrically dominant core. The technique is demonstrated with a core–shell colloid composed of a 135 nm crosslinked polystyrene (PS) core coated with a ca. 10 nm thick uncrosslinked poly(methyl acrylate-co-propargyl acrylate) shell. Due to the applicability of this technique for generating particles useful in biomedical imaging or drug delivery applications, the core–shell particles are surface modified with a variety of azide-terminated poly(ethylene glycol) (PEG) derivatives, including a poloxamer which was terminated on either end by an azide and a naphthalimide chromophore. The resulting fluorescent particles had an absorbance at 413 nm and peak emission at 525 nm. The PEG derivatives could be attached to the particles at a grafting density of ca. 0.2–0.3 groups/nm2.

Reversible crosslinking density stimulated diffraction wavelength tuning of hydrogel-encapsulated crystalline colloidal arrays

The reversible variation in the observed stop band of a hydrogel-encapsulated crystalline colloidal array was achieved through the selective formation and destruction of -S-Pb-S- linkages within the hydrogel. A reversible 45 nm stop band shift could be achieved with a cyclical treatment of Pb(2+) and then dithiothreitol solution.

Comparative study on the effect of thermal annealing on polymer/small molecule blend and copolymer light-emitting devices

The intrinsic deterioration in device performance of polymeric single layer OLEDs that were doped with a fluorescent emitter was studied. The specific focus was on the role that thermal aging, at sub-glass transition temperatures of the polymeric layer, has on the phase separation of the active layer. This was accomplished by the rational design of an oxadiazole-containing methylacrylate monomer that was energetically similar to the technologically important electron- transporting small molecule 2-biphenyl-4-yl-5-(4-tert-butylphenyl)-1,3,4- oxadiazole (tBu-PBD). This monomer was copolymerized with a carbazole containing hole-transporting monomer 2-(9H-carbazol-9-yl)ethyl 2-methylacrylate (CE) and the resulting copolymer was utilized as the active layer with coumarin 6. With coumarin 6, the devices exhibited a stable mean luminance of ca. 400 cd/m2 with thermal aging at temperatures ranging from 23 °C to 130 °C, while a comparable poly(9-vinyl-9H-carbazole)/tBu-PBD blend device exhibited a drop from an initial mean luminance of 2500 cd/m2 to 1.6 cd/m2. The reduction in luminance and luminance efficiency for the blend system was attributed to phase separation in the blend.