Influence of intermolecular interactions on spectroscopic characteristics of metal nanoparticles and their composites.

In this paper we investigate the possibility to apply the concepts of non-specific intermolecular interactions and dispersive local field effect approach for study of the influence of interactions of metal nanoparticles with matrix molecules on the spectral characteristics of composites. The effect of intermolecular (interparticle) interactions and the influence of the dielectric environment on the peak position of the plasmon resonance band of colloidal solutions and thin films formed from noble metal nanostructures is determined. Simulated and experimental absorption spectra obtained for a colloidal solution of silver and gold nanoparticles, of various shapes and sizes in water and glycerol, are in good agreement.

Heparin conjugated quantum dots for in vitro imaging applications.

In this work heparin-gelatine multi-layered cadmium telluride quantum dots (QDgel/hep) were synthesised using a novel 'one-pot' method. The QDs produced were characterised using various spectroscopic and physiochemical techniques. Suitable QDs were then selected and compared to thioglycolic acid stabilised quantum dots (QDTGA) and gelatine coated quantum dots (QDgel) for utilisation in in vitro imaging experiments on live and fixed permeabilised THP-1, A549 and Caco-2 cell lines. Exposure of live THP-1 cells to QDgel/hep resulted in localisation of the QDs to the nucleus of the cells. QDgel/hep show affinity for the nuclear compartment of fixed permeabilised THP-1 and A549 cells but remain confined to cytoplasm of fixed permeabilised Caco-2 cells. It is postulated that heparin binding to the CD11b receptor facilitates the internalisation of the QDs into the nucleus of THP-1 cells. In addition, the heparin layer may reduce the unfavourable thrombogenic nature of quantum dots observed in vivo. FROM THE CLINICAL EDITOR: In this study, heparin conjugated quantum dots were found to have superior imaging properties compared to its native counterparts. The authors postulate that heparin binding to the CD11b receptor facilitates QD internalization to the nucleus, and the heparin layer may reduce the in vivo thrombogenic properties of quantum dots.

Experimental and theoretical investigation of the distance dependence of localized surface plasmon coupled Förster resonance energy transfer.

The distance dependence of localized surface plasmon (LSP) coupled Förster resonance energy transfer (FRET) is experimentally and theoretically investigated using a trilayer structure composed of separated monolayers of donor and acceptor quantum dots with an intermediate Au nanoparticle layer. The dependence of the energy transfer efficiency, rate, and characteristic distance, as well as the enhancement of the acceptor emission, on the separations between the three constituent layers is examined. A d(-4) dependence of the energy transfer rate is observed for LSP-coupled FRET between the donor and acceptor planes with the increased energy transfer range described by an enhanced Förster radius. The conventional FRET rate also follows a d(-4) dependence in this geometry. The conditions under which this distance dependence is valid for LSP-coupled FRET are theoretically investigated. The influence of the placement of the intermediate Au NP is investigated, and it is shown that donor-plasmon coupling has a greater influence on the characteristic energy transfer range in this LSP-coupled FRET system. The LSP-enhanced Förster radius is dependent on the Au nanoparticle concentration. The potential to tune the characteristic energy transfer distance has implications for applications in nanophotonic devices or sensors.

A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells.

Gold nanomaterials are currently raising a significant interest for human welfare in the field of clinical diagnosis, therapeutics for chronic pathologies, as well as of many other biomedical applications. In particular, gold nanomaterials are becoming a promising technology for developing novel approaches and treatments against widespread societal diseases such as cancer. In this study, we investigated the potential of proprietary gold nanoboxes (AuNBs) as carriers for their perspective translation into multifunctional, pre-clinical nano-enabled systems for personalized medicine approaches against lung cancer. A safe-by-design, tiered approach, with systematic tests conducted in the early phases on uncoated AuNBs and more focused testing on the coated, drug-loaded nanomaterial toward the end, was adopted. Our results showed that uncoated AuNBs could effectively penetrate into human lung adenocarcinoma (A549) cells when in simple (mono-cultures) or complex (co- and three-dimensional-cultures) in vitro microenvironments mimicking the alveolar region of human lungs. Uncoated AuNBs were biologically inert in A549 cells and demonstrated signs of biodegradability. Concurrently, preliminary data revealed that coated, drug-loaded AuNBs could efficiently deliver a chemotherapeutic agent to A549 cells, corroborating the hypothesis that AuNBs could be used in the future for the development of personalized nano-enabled systems for lung cancer treatment.

Wavelength, concentration, and distance dependence of nonradiative energy transfer to a plane of gold nanoparticles.

Nonradiative energy transfer to metal nanoparticles is a technique used for optical-based distance measurements which is often implemented in sensing. Both Förster resonant energy transfer (FRET) and nanometal surface energy transfer (NSET) mechanisms have been proposed for emission quenching in proximity to metal nanoparticles. Here quenching of emission of colloidal quantum dots in proximity to a monolayer of gold nanoparticles is investigated. Five differently sized CdTe quantum dots are used to probe the wavelength dependence of the quenching mechanism as their emission peak moves from on resonance to off resonance with respect to the localized surface plasmon peak of the gold nanoparticle layer. The gold nanoparticle concentration and distance dependences of energy transfer are discussed. Photoluminescence quenching and lifetime data are analyzed using both FRET and NSET models and the extracted characteristic distances are compared with theory. Good agreement with FRET theory has been found for quantum dots with emission close to the localized surface plasmon resonance, though larger than expected Förster radii are observed for quantum dots with emission red-shifted with respect to the localized surface plasmon peak. Closer agreement between experimental and theoretical characteristic distances can be found across the full wavelength range within a NSET approach.

Evaluating the potential of quantum dots for in vitro biological studies: effects on gene expression using microarray analysis.

Quantum dots have potential applications in the biomedical field and especially in bioimaging owing to their tunable fluorescent properties. Although many phenotypic studies have been carried out using QDs on different cell lines, only very few of them involved the analysis of the effect of QDs on gene expression. Here, we describe the application of microarray gene expression analysis for studying the differential expression of genes in the cells treated with QDs.

Synthesis of biocompatible gelatinated thioglycolic acid-capped CdTe quantum dots ("jelly dots").

Semiconductor luminescent Quantum Dots (QDs) constitute a growing area of research for biological imaging and other biomedical applications. One of the main challenges is to provide QDs with a biocompatible and easy to functionalize surface while retaining the core optical properties. Gelatine is an excellent candidate for that purpose as it is a very common natural polymer, highly biocompatible and bearing various functional groups. Here we present a simple, one-pot method for manufacturing gelatinated QDs with chosen optical properties.

Multifactorial determinants that govern nanoparticle uptake by human endothelial cells under flow.

Vascular endothelium is a potential target for therapeutic intervention in diverse pathological processes, including inflammation, atherosclerosis, and thrombosis. By virtue of their intravascular topography, endothelial cells are exposed to dynamically changing mechanical forces that are generated by blood flow. In the present study, we investigated the interactions of negatively charged 2.7 nm and 4.7 nm CdTe quantum dots and 50 nm silica particles with cultured endothelial cells under regulated shear stress (SS) conditions. Cultured cells within the engineered microfluidic channels were exposed to nanoparticles under static condition or under low, medium, and high SS rates (0.05, 0.1, and 0.5 Pa, respectively). Vascular inflammation and associated endothelial damage were simulated by treatment with tumor necrosis factor-α (TNF-α) or by compromising the cell membrane with the use of low Triton X-100 concentration. Our results demonstrate that SS is critical for nanoparticle uptake by endothelial cells. Maximal uptake was registered at the SS rate of 0.05 Pa. By contrast, endothelial exposure to mild detergents or TNF-α treatment had no significant effect on nanoparticle uptake. Atomic force microscopy demonstrated the increased formation of actin-based cytoskeletal structures, including stress fibers and membrane ruffles, which have been associated with nanoparticle endocytosis. In conclusion, the combinatorial effects of SS rates, vascular endothelial conditions, and nanoparticle physical and chemical properties must be taken into account for the successful design of nanoparticle-drug conjugates intended for parenteral delivery.

Effects of long-term exposure of gelatinated and non-gelatinated cadmium telluride quantum dots on differentiated PC12 cells.

BACKGROUND: The inherent toxicity of unmodified Quantum Dots (QDs) is a major hindrance to their use in biological applications. To make them more potent as neuroprosthetic and neurotherapeutic agents, thioglycolic acid (TGA) capped CdTe QDs, were coated with a gelatine layer and investigated in this study with differentiated pheochromocytoma 12 (PC12) cells. The QD--cell interactions were investigated after incubation periods of up to 17 days by MTT and APOTOX-Glo Triplex assays along with using confocal microscopy. RESULTS: Long term exposure (up to 17 days) to gelatinated TGA-capped CdTe QDs of PC12 cells in the course of differentiation and after neurites were grown resulted in dramatically reduced cytotoxicity compared to non-gelatinated TGA-capped CdTe QDs. CONCLUSION: The toxicity mechanism of QDs was identified as caspase-mediated apoptosis as a result of cadmium leaking from the core of QDs. It was therefore concluded that the gelatine capping on the surface of QDs acts as a barrier towards the leaking of toxic ions from the core QDs in the long term (up to 17 days).

Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics.

BACKGROUND: Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). RESULTS: The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. CONCLUSIONS: The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics.

Surface plasmon enhanced energy transfer between donor and acceptor CdTe nanocrystal quantum dot monolayers.

Surface plasmon enhanced Förster resonant energy transfer (FRET) between CdTe nanocrystal quantum dots (QDs) has been observed in a multilayer acceptor QD-gold nanoparticle-donor QD sandwich structure. Compared to a donor-acceptor QD bilayer structure without gold nanoparticles, the FRET rate is enhanced by a factor of 80 and the Förster radius increases by 103%. Furthermore, a strong impact of the donor QD properties on the surface plasmon mediated FRET is reported.

Plasmon-induced CD response of oligonucleotide-conjugated metal nanoparticles.

Non-chiral metal nanoparticles conjugated with chiral oligonucleotide molecules demonstrated a circular dichroism (CD) at the plasmonic wavelengths due to aggregation effects.

Energy transfer in colloidal CdTe quantum dot nanoclusters.

Quantum dot (QD) nanoclusters were formed using oppositely charged colloidal CdTe QDs, of two different sizes, mixed in aqueous solutions. The photoluminescence (PL) spectra and time-resolved PL decays show signatures of Förster resonant energy transfer (FRET) from the donor QDs to the acceptor QD in the nanoclusters. A concentration dependence of the donor QD lifetime is observed in mixed solutions with a donor: acceptor ratio greater than 1:1. The concentration dependent time-resolved PL data indicate different regimes of cluster formation, with evidence for donor-to-donor FRET in the larger donor-acceptor nanoclusters and evidence for the formation of all-donor clusters in mixed solutions with high donor concentrations.

Long-term exposure of CdTe quantum dots on PC12 cellular activity and the determination of optimum non-toxic concentrations for biological use.

BACKGROUND: The unique and tuneable photonic properties of Quantum Dots (QDs) have made them potentially useful tools for imaging biological entities. However, QDs though attractive diagnostic and therapeutic tools, have a major disadvantage due to their inherent cytotoxic nature. The cellular interaction, uptake and resultant toxic influence of CdTe QDs (gelatinised and non-gelatinised Thioglycolic acid (TGA) capped) have been investigated with pheochromocytoma 12 (PC12) cells. In conjunction to their analysis by confocal microscopy, the QD - cell interplay was explored as the QD concentrations were varied over extended (up to 72 hours) co-incubation times. Coupled to this investigation, cell viability, DNA quantification and cell proliferation assays were also performed to compare and contrast the various factors leading to cell stress and ultimately death. RESULTS: Thioglycolic acid (TGA) stabilised CdTe QDs (gel and non - gel) were co-incubated with PC12 cells and investigated as to how their presence influenced cell behaviour and function. Cell morphology was analysed as the QD concentrations were varied over co-incubations up to 72 hours. The QDs were found to be excellent fluorophores, illuminating the cytoplasm of the cells and no deleterious effects were witnessed at concentrations of ~10-9 M. Three assays were utilised to probe how individual cell functions (viability, DNA quantification and proliferation) were affected by the presence of the QDs at various concentrations and incubation times. Cell response was found to not only be concentration dependant but also influenced by the surface environment of the QDs. Gelatine capping on the surface acts as a barrier towards the leaking of toxic atoms, thus reducing the negative impact of the QDs. CONCLUSION: This study has shown that under the correct conditions, QDs can be routinely used for the imaging of PC12 cells with minimal adverse effects. We have found that PC12 cells are highly susceptible to an increased concentration range of the QDs, while the gelatine coating acts as a barrier towards enhanced toxicity at higher QD concentrations.