Yuriy P. Bandera

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.

A versatile stable platform for multifunctional applications: synthesis of a nitroDOPA–PEO–alkyne scaffold for iron oxide nanoparticles

Contemporary magnetic nanoparticle composites are individually designed for specific biomedical applications. We describe the syntheses and characterization of a heterobifunctional polyethylene oxide (PEO) using nitroDOPA as a robust anchoring group on one end and an alkyne as the reactive surface for additional application specific modification.

Design rules for carbazole derivatized n-alkyl methacrylate polymeric memristors

The alternating current (AC) and direct current (DC) electrical response of a number of n-alkyl methacrylate polymers with a charge transporting pendant carbazole ring were studied. The electrical properties of the polymers were studied as a function of the n-alkyl length with n ranging from 2 to 11. The DC current (I)–voltage (V) response of the polymers was characterized by an erratic and bistable response, while their AC I–V response was a pinched hysteresis loop when measured between 1–100 Hz. For polymers with n < 9, their pinched hysteresis loop was characterized by “jump transitions” indicative of bistability, while polymers with n ≥ 9 had a pinched hysteresis loop that was smooth in appearance. Dielectric spectroscopy on the polymers indicated that as the n-alkyl length is increased, the rotation flexibility of the carbazole moiety is enhanced. The n-alkyl methacrylate polymers with a pendant carbazole ring spaced n ≥ 9 exhibited a lower activation energy and temperature for the onset of ring motion and resulted in polymer-based memristors that exhibited electrical characteristics, such as incrementally adjustable conductivity and are potential candidates for mimicking synaptic plasticity.

Reducing background noise in near-infrared medical imaging: Routes to activated fluorescing

Activated fluorescence was achieved for nanoparticle based systems. One particulate system consisting of a poly(propargyl acrylate) (PA) core with covalently attached derivatized fluorescein and modified bovine serum albumin covalently conjugated to a cyanine 3 derivative was initially nonfluorescent. Upon trypsin addition and subsequent proteolytic digestion, Förster resonance energy transfer (FRET) was induced. The other particulate system consisted of a PA core with covalently attached azide modified BSA, which was covalently attached to a silicon phthalocyanine derivative (PA/BSA/akSiPc600). Both systems were biocompatible. To investigate activated fluorescence with the PA/BSA/akSiPc600 system in cancer cells, human non-small cell lung cancer cells (A549 cell line) were used as a model system. The PA/BSA/akSiPc600 system was incubated with the cells at varying time points in an effort to see a fluorescence increase over time as the cells uptake the particles and as they digest the BSA, most probably, via endocytosis. It was seen, through live cell scanning confocal microscopy, that the fluorescence was activated in the cell.

Asymmetric electrically conducting element printed from aqueously dispersed pentacene nanoparticles

Pentacene is an organic semiconductor with promising electronic properties, but it has been severely limited in application due to difficult and expensive processing. (Microelectron Eng, 88, 9, 2959–2963, 2011), (J Appl Phys, 109, 8, 083710, 2011) Generally, pentacene-based devices typically require high-vacuum processing, and/or synthetic modifications to the molecule must be incorporated. (Thin Solid Films, 427, 1-2, 367–370, 2003), (J Am Chem Soc, 129, 34, 10,308–10,309, 2007), (J Mater Chem C, 1, 11, 2193–2201, 2013), (ACS Nano, 7, 9, 7983–7991, 2013) We developed a technique to transform small molecule pentacene into an aqueously dispersed particulate material. Pentacene was introduced into a miniemulsion reaction and formed into nano-scale platelet-like particles. After the miniemulsion, the emulsified pentacene showed indefinite stability in the aqueous phase, which is key in a material used for printable electronics. Devices fabricated from the aqueously dispersed particles demonstrated behavior similar to a Zener diode with a breakdown voltage of ≈ 2 VDC.

Sequestering survivin to functionalized nanoparticles

Survivin belongs to the family of inhibitor of apoptosis proteins (IAP) and is present in most cancers while being below detection limits in most terminally differentiated adult tissues, making it an attractive protein to target for diagnostic and, potentially, therapeutic roles. Sub-100 nm poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of an azide-terminated survivin ligand derivative (azTM) originally proposed by Abbott Laboratories and speculated to bind directly to survivin (protein) at its dimer interface. Using affinity pull-down studies, it was determined that the PA/azTM nanoparticles selectively bind survivin and the particles can enhance apoptotic cell death in glioblastoma cell lines and other survivin over-expressing cell lines such as A549 and MCF7 relative to cells incubated with the original Abbott-derived small molecule inhibitor.

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.