Sub-Millisecond Response Time in a Photorefractive Composite Operating under CW Conditions.

Extensive study of photorefractive polymeric composites photosensitized with semiconductor nanocrystals has yielded data indicating that the inclusion of such nanocrystals enhances the charge-carrier mobility, and subsequently leads to a reduction in the photorefractive response time. Unfortunately, the included nanocrystals may also act as a source of deep traps, resulting in diminished diffraction efficiencies as well as reduced two beam coupling gain coefficients. Nonetheless, previous studies indicate that this problem is mitigated through the inclusion of semiconductor nanocrystals possessing a relatively narrow band-gap. Here, we fully exploit this property by doping PbS nanocrystals into a newly formulated photorefractive composite based on molecular triphenyldiamine photosensitized with C60. Through this approach, response times of 399 µs are observed, opening the door for video and other high-speed applications. It is further demonstrated that this improvement in response time occurs with little sacrifice in photorefractive efficiency, with internal diffraction efficiencies of 72% and two-beam-coupling gain coefficients of 500 cm(-1) being measured. A thorough analysis of the experimental data is presented, supporting the hypothesized mechanism of enhanced charge mobility without the accompaniment of superfluous traps. It is anticipated that this approach can play a significant role in the eventual commercialization of this class of materials.

Specific intracellular uptake of herceptin-conjugated CdSe/ZnS quantum dots into breast cancer cells.

Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). The mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. The in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. To clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined by confocal laser scanning microscopy. As a result, the QD-Her bound specifically to the membrane of SK-BR3, which became almost saturated after 6 hours incubation. This suggests that the growth signal of breast cancer cells is inhibited completely by the specific binding of herceptin to the Her-2 receptor of SK-BR3 membrane, resulting in cell death.

Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties.

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials.

Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1µM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications.

Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism.

Functional peptides that transfer biomaterials, such as semiconductor quantum dots (QDs), into cells in biomaterial research have been developed in recent years. Delivery of QDs conjugated with cell-penetrating peptides (CPPs) into cells by the endocytic pathway was problematic in biomedical applications because of lysosomal trapping. Here, we demonstrate that histidine- and arginine-rich CPPs (HR9 peptides) stably and noncovalently combined with QDs are able to enter into cells in an extremely short period (4 min). Interrupting both F-actin polymerization and active transport did not inhibit the entry of HR9/QD complexes into cells, indicating that HR9 penetrates cell membrane directly. Subcellular colocalization studies indicated that QDs delivered by HR9 stay in cytosol without any organelle capture. Dimethyl sulphoxide, ethanol and oleic acid, but not pyrenebutyrate, enhanced HR9-mediated intracellular delivery of QDs by promoting the direct membrane translocation pathway. HR9 and HR9/QDs were not cytotoxic. These findings suggest that HR9 could be an efficient carrier to deliver drugs without interfering with their therapeutic activity.

Nona-arginine facilitates delivery of quantum dots into cells via multiple pathways.

Semiconductor quantum dots (QDs) have recently been used to deliver and monitor biomolecules, such as drugs and proteins. However, QDs alone have a low efficiency of transport across the plasma membrane. In order to increase the efficiency, we used synthetic nona-arginine (SR9), a cell-penetrating peptide, to facilitate uptake. We found that SR9 increased the cellular uptake of QDs in a noncovalent binding manner between QDs and SR9. Further, we investigated mechanisms of QD/SR9 cellular internalization. Low temperature and metabolic inhibitors markedly inhibited the uptake of QD/SR9, indicating that internalization is an energy-dependent process. Results from both the pathway inhibitors and the RNA interference (RNAi) technique suggest that cellular uptake of QD/SR9 is predominantly a lipid raft-dependent process mediated by macropinocytosis. However, involvement of clathrin and caveolin-1 proteins in transducing QD/SR9 across the membrane cannot be completely ruled out.

Study of uptake and loss of silica nanoparticles in living human lung epithelial cells at single cell level.

The toxicology of nanomaterials is a blooming field of study, yet it is difficult to keep pace with the innovations in new materials and material applications. Those applications are quickly being introduced in research, industrial, and consumer settings. Even though the cytotoxicity of many types of nanoparticles has been demonstrated, the behavior of those particles in a biological environment is not yet fully known. This work characterized the following over time: protein adsorption on silica particle surfaces, the internalization of particles in human lung carcinoma (A549) cells when coated with different specific proteins or no proteins at all, and the cellular loss of particles following the removal of extracellular particles. Proteins were shown to quickly saturate the particle surface, followed by a competitive process of particle agglomeration and protein adsorption. Uptake of particles peaked at 8-10 h, and it was determined that, in this system, the charge of the protein-coated particles changed the rate of uptake if the charge difference was great enough. Cells internalized particles lacking any adsorbed proteins with approximately 3 times the rate of protein-coated particles with the same charge. Although particles exited cells over time, the process was slower than uptake and did not near completion within 24 h. Finally, analysis at the single cell level afforded observations of particle agglomerates loosely associated with cell membranes when serum was present in the culture medium, but in the absence of serum, particles adhered to the dish floor and formed smaller agglomerates on cell surfaces. Although data trends were easily distinguished, all samples showed considerable variation from cell to cell.

Photorefractivity in a polymeric composite photosensitized with NiS nanocrystals.

The photorefractive performance of a polymeric composite photosensitized through the inclusion of NiS nanocrystals is described. The nanocrystals were characterized using visible-absorption spectroscopy, energy-dispersive x-ray spectroscopy, and transmission electron microscopy. We further demonstrate the ability to enhance various aspects of the composite's photorefractive performance by performing ligand exchange on the nanocrystals prior to their incorporation into the polymer composite. This procedure resulted in a lowering of the overmodulation voltage from approximately 70 to approximately 50 V/microm without affecting the maximum diffraction efficiency of approximately 40%. An increase in the two-beam-coupling gain coefficient was similarly observed, increasing from 38 to 79 cm(-1). The photoconductivities were used in determining the overall quantum efficiencies associated with the photorefractive devices. All experiments were conducted at 633 nm and the data represent a significant improvement in the photorefractive performance of inorganic-organic hybrid photorefractive materials.

Beam cleanup and image restoration with a photorefractive polymeric composite.

We demonstrate, for the first time to our knowledge, the use of a photorefractive polymeric composite to clean a phase-distorted laser beam and reconstruct a badly distorted image. Advantageous qualities including relatively high figures of merit, ease of processability, and low cost make this class of materials attractive when compared with their inorganic crystalline counterparts. In addition, we used four-wave-mixing and holographic techniques to obtain an internal diffraction efficiency of approximately 31% at 54.5 V/micron and a two-beam-coupling gain coefficient of gamma = 17 cm-1 at 54.5 V/micron under our experimental conditions.

Dynamic correction of a distorted image using a photorefractive polymeric composite.

We demonstrate, for the first time, the dynamic correction of aberrated images in real-time using a polymeric composite with fast response times. The current novel experimental design is capable of restoring a phase aberrated, image carrying laser beam, to nearly its original quality. The ability to reconstruct images in real-time is demonstrated through the changing of the aberrating medium at various speeds. In addition, this technique allows for the correction of images in motion, demonstrated through the oscillatory movement of the resolution target. We also have demonstrated that important parameters of the materials in the study such as response times, diffraction efficiencies and optical gains all retain high figures of merit values under the current experimental conditions.

Photorefractive inorganic organic polymer-dispersed liquid-crystal nanocomposite photosensitized with cadmium sulfide quantum dots.

We report on a new photorefractive medium consisting of a hole-transporting polymer composite matrix, electro-optically active nanodroplets of liquid crystals, and cadmium sulfide quantum dots as photosensitizers. This medium exhibits greater than 90% internal diffraction efficiency and a net two-beam coupling gain of 22.5 cm(-1) with a response time of <1 min . Data on optical transmission are also presented.