Academic literature on the topic 'Biomedical labeling - Semiconductor Nanocrystals'

Recently, the drugs in nanometer size range have found to increase the performance of various dosage forms. Quantum dots (QDs) have gained attention and interest of scientists due to their targeting and imaging potential in nano based drug delivery, in pharmaceutical and biomedical (cell biology) applications. They are artificial semiconductor nanocrystals that have tunable and efficient photo luminescence with narrow emission spectra and high light stability making them excellent probes for bioimaging applications. QDs absorb white light and can produce different colors determined by the size of the particles and band Gap. Nowadays, quantum dots are used for labeling live biological material in vitro and in vivo in animals (other than humans) for research purposes and also useful for immunoassay studies. In the present article, we have discussed various aspects of QDs, highlighting their pharmaceutical and biomedical applications and current challenges in introducing QDs into clinical practice.

Adipose tissue-derived stem cells (ASCs) have a self-renewing ability and can be induced to differentiate into various types of mesenchymal tissue. Because of their potential for clinical application, it has become desirable to label the cells for tracing transplanted cells and for in vivo imaging. Quantum dots (QDs) are novel inorganic probes that consist of CdSe/ZnS-core/shell semiconductor nanocrystals and have recently been explored as fluorescent probes for stem cell labeling. In this study, negatively charged QDs655 were applied for ASCs labeling, with the cationic liposome, Lipofectamine. The cytotoxicity of QDs655-Lipofectamine was assessed for ASCs. Although some cytotoxicity was observed in ASCs transfected with more than 2.0 nM of QDs655, none was observed with less than 0.8 nM. To evaluate the time dependency, the fluorescent intensity with QDs655 was observed until 24 h after transfection. The fluorescent intensity gradually increased until 2 h at the concentrations of 0.2 and 0.4 nM, while the intensity increased until 4 h at 0.8 nM. The ASCs were differentiated into both adipogenic and osteogenic cells with red fluorescence after transfection with QDs655, thus suggesting that the cells retain their potential for differentiation even after transfected with QDs655. These data suggest that QDs could be utilized for the labeling of ASCs.

The novel optical and electrical properties of luminescent semiconductor nanocrystals are appealing for ultrasensitive multiplexing and multicolor applications in a variety of fields, such as biotechnology, nanoscale electronics, and opto-electronics. Luminescent CdSe and CdTe nanocrystals are archetypes for this dynamic research area and have gained interest from diverse research communities. In this review, we first describe the advances in preparation of size- and shape-controlled CdSe and CdTe semiconductor nanocrystals with the organometallic approach. This article gives particular focus to water soluble nanocrystals due to the increasing interest of using semiconductor nanocrystals for biological applications. Post-synthetic methods to obtain water solubility, the direct synthesis routes in aqueous medium, and the strategies to improve the photoluminescence efficiency in both organic and aqueous phase are discussed. The shape evolution in aqueous medium via self-organization of preformed nanoparticles is a versatile and powerful method for production of nanocrystals with different geometries, and some recent advances in this field are presented with a qualitative discussion on the mechanism. Some examples of CdSe and CdTe nanocrystals that have been applied successfully to problems in biosensing and bioimaging are introduced, which may profoundly impact biological and biomedical research. Finally we present the research on the use of luminescent semiconductor nanocrystals for construction of light emitting diodes, solar cells, and chemical sensors, which demonstrate that they are promising building blocks for next generation electronics.

Abstract Raman spectroscopy is a powerful method that gives insight into the atomic structure and composition of nanomaterials, but also allows to draw conclusions about their electronic properties. It is based on the inelastic scattering of light, which is able to excite phonons in the material. In the field of semiconductor nanocrystals, Raman spectroscopy has been employed to make significant contributions to the analysis of lattice distortion, interfaces, phase mixing, and defect formation. Yet, there is no clear consensus on how the electronic and crystal structure of the material interacts with the incident light to yield the observed spectra. This review gives a brief overview over the method. It then reviews the most important findings, current developments, and discusses the efforts to formulate a consistent model that allows to establish the method as a tool for structural analysis.

Chitosan coated ZnSe:Mn (CS-ZnSe:Mn) nanocrystals were successfully synthesized in aqueous system through a γ-radiation route at room temperature under ambient pressure. The structure and properties of nanocrystals were investigated with transmission electron microscope (TEM), fourier transform infrared spectrometer (FT-IR), ultraviolet-visible (UV-vis) spectrometer, photoluminescence emission (PL) spectra, X-ray Diffraction (XRD) and energy dispersion spectrum (EDS). Results showed that the diameter of these nanocrystals was about 4 nm with narrow size distribution. With the increase of doped Mn2+ concentration, strong emission peak at 610 nm was observed besides the weak emission peak at 425 nm since the non-radiative transition of 4T1(4G)–6A1(6S) level, resulting the transfer of fluorescence color from blue to orange. Moreover, analysis of SQUID magnetometer indicated that the nanocrystals were superparamagnetic with a saturation magnetization of 1.7 emu/g and a Curie-Weiss temperature of 14–15 K. Hep G2 cells were incubated in solution of nanocrystals and results showed that the synthesized nanocrystals could stain cytoplasm but could not enter into nucleus.

AbstractPlasmonic nanoparticles have become a popularly accepted research tool in optoelectronics, photonics, and biomedical applications. The relatively recently appearing semiconductor plasmonic nanoparticles, as opposed to metal ones, are characterized by infrared plasmonic optical transitions and their application has a great future. In this work, the possibility of conversion of semiconductor (excitonic) fluorescence nanocrystals, i.e., quantum dots of the CuInS_2 composition, to plasmonic nanoparticles by postsynthetic treatment without changes in the chemical composition of inorganic part of the nanocrystals was demonstrated for the first time ever.

Metal-oxide-semiconductor structures with NiSi2 and CoSi2 nanocrystals embedded in the SiO2 layer have been fabricated. A pronounced capacitance–voltage hysteresis was observed with a memory window about 1 V under low programming voltage. The retention characteristic can be improved by using HfO2 layer as control oxide. The processing of the structure is compatible with the current manufacturing technology of semiconductor industry.

One area of interest in nanotechnology, particularly in nanobiotechnology, is the study of optical and electrical phenomena related to nanometer-scale semiconductors. Quantum dots (QDs) are semiconductor nanocrystals whose electrons and holes are quantum-confined in all three spatial dimensions. QDs’ unique optical features make them suitable for use as optical probes or as optically trackable biomolecule carriers for in vitro and in vivo research in biological applications. QDs can be used to target specific areas in vitro and in vivo by conjugating relevant functional biomolecules onto their surfaces. This chapter comprehensively describes the different aspects of QDs’ applications in the field of biomedical diagnosis.

Semiconductor nanocrystals have unique optical properties due to quantum confinement effects, and a variety of promising approaches have been devised to interface the nanomaterials with biomolecules for bioimaging and therapeutic applications. Such bio-interface can be facilitated via a DNA template for nanoparticles as oligonucleotides can mediate the aqueous-phase nucleation and capping of semiconductor nanocrystals.[1,2] Here, we report a novel scheme of synthesizing fluorescent nanocrystal quantum dots (NQDs) using DNA aptamers and the use of this biotic/abiotic nanoparticle system for growth inhibition of MCF-7 human breast cancer cells for the first time. Particularly, we used two DNA sequences for this purpose, which have been developed as anti-cancer agents: 5-GGT GGT GGT GGT TGT GGT GGT GGT GG-3 (also called, AGRO) and 5-(GT)15-3.[3–5] This study may ultimately form the basis of unique nanoparticle-based therapeutics with the additional ability to optically report molecular recognition. Figure 1a shows the photoluminescence (PL) spectra of GT- and AGRO-passivated PbS QD that fluoresce in the near IR, centered at approximately 980 nm. A typical synthesis procedure involves rapid addition of sodium sulfide in the mixture solution of DNA and Pb acetate at a molar ratio of 2:4:1. The resulting nanocrystals are washed to remove unreacted DNA and ions by adding mixture solution of NaCl and isopropanol, followed by centrifugation. The precipitated nanocrystals are collected and re-suspended in aqueous solution by mild sonication. Optical absorption measurements reveal that approximately 90 and 77% of GT and AGRO DNA is removed after the washing process. The particle size distribution in Figure 1b suggests that the GT sequence-capped PbS particles are primarily in 3–5 nm diameter range. These nanocrystals can be easily incorporated with mammalian cells and remain highly fluorescent in sub-cellular environments. Figure 1c serially presents an optical image of a MCF-7 cell and a PL image of the AGRO-capped QD incorporated with the cell. Figure 1. (a) Normalized fluorescence spectra of PbS QD synthesized with GT and AGRO sequences, which were previously developed as anti-cancer agents. The DNA-capped QD fluoresce in the near IR centered at ∼980 nm. (b) TEM image of GT-templated nanocrystals ranging 3–5 nm in diameter. (c) Optical image of an MCF-7 human breast cancer cell after a 12-hour exposure to aptamer-capped QD. (d) PL image of AGRO-QD incorporated with the cell, indicating that these nanocrystals remain highly fluorescent in sub-cellular environments. One immediate concern for interfacing inorganic nanocrystals with cells and tissue for labeling or therapeutics is their cytotoxicity. The nanoparticle cytotoxicity is primarily determined by material composition and surface chemistry, and QD are potentially toxic by generating reactive oxygen species or by leaching heavy metal ions when decomposed.[6] We examined the toxicity of aptamer-passivated nanocrystals with NIH-3T3 mouse fibroblast cells. The cells were exposed to PbS nanocrystals for 2 days before a standard MTT assay as shown in Figure 2, where there is no apparent cytotoxicity at these doses. In contrast, Pb acetate exerts statistically significant toxicity. This observation suggests a stable surface passivation by the DNA aptamers and the absence of appreciable Pb2+ leaching. Figure 2. Viability of 3T3 mouse fibroblast cells after a 2-day exposure to DNA aptamer-capped nanocrystals. There is no apparent dose-dependent toxicity, whereas a statistically significant reduction in cell viability is observed with Pb ions. Note that Pb acetate at 133 μM is equivalent to the Pb2+ amount that was used for PbS nanocrystal synthesis at maximum concentration. Error bars are standard deviations of independent experiments. *Statistically different from control (p<0.005). Finally, we examined if these cyto-compatible nanoparticle-aptamers remained therapeutically active for cancer cell growth inhibition. The MTT assay results in Figure 3a show significantly decreased growth of breast cancer cells incorporated with AGRO, GT, and the corresponding templated nanocrystals, as anticipated. In contrast, 5-(GC)15-3 and the QDs synthesized with the same sequence, which were used as negative controls along with zero-dose control cells, did not alter cell viability significantly. Here, we define the growth inhibition efficacy as (100 − cell viability) per DNA of a sample, because the DNA concentration is significantly decreased during the particle washing. The nanoparticle-aptamers demonstrate 3–4 times greater therapeutic activities compared to the corresponding aptamer drugs (Figure 3b). We speculate that when a nanoparticle-aptamer is internalized by the cancer cells, it forms an intracellular complex with nucleolin and nuclear factor-κB (NF-κB) essential modulator, thereby inhibiting NF-κB activation that would cause transcription of proliferation and anti-apoptotic genes.[7] The nanoparticle-aptamers may more effectively block the pathways for creating anti-apoptotic genes or facilitate the cellular delivery of aptamers via nanoparticle uptake. Our additional investigation indicates that the same DNA capping chemistry can be utilized to produce aptamer-mediated Fe3O4 nanocrystals, which may be potentially useful in MRI and therapeutics, considering their magnetic properties and biocompatibility. In summary, the nanoparticle-based therapeutic schemes developed here should be valuable in developing a multifunctional drug delivery and imaging agent for biological systems. Figure 3. Anti-proliferation of MCF-7 human breast cancer cells with aptamer-passivated nanocrystals. (a) Viability of MCF-7 cells exposed to AGRO and GT sequences, and AGRO-/GT-capped QD for 7 days. The DNA concentration was 10 uM, while the particles were incubated with cells at 75 nM. (b) Growth inhibition efficacy is defined as (100 − cell viability) per DNA to correct the DNA concentration after particle washing.

Semiconductor and magnetic nanoparticles hold unique optical and magnetic properties, and great promise for bio-imaging and therapeutic applications. As part of their stable synthesis, the nanocrystal surfaces are usually capped by long chain organic moieties such as trioctylphosphine oxide. This capping serves two purposes: it saturates dangling bonds at the exposed crystalline lattice, and it prevents irreversible aggregation by stabilizing the colloid through entropic repulsion. These nanocrystals can be rendered water-soluble by either ligand exchange or overcoating, which hampers their widespread use in biological imaging and biomedical therapeutics. Here, we report a novel scheme of synthesizing fluorescent PbS and magnetic Fe3O4 nanoparticles using DNA oligonucleotides. Our method of PbS synthesis includes addition of Na2S to the mixture solution of DNA sequence and Pb acetate (at a fixed molar ratio of DNA/S2−/Pb2+ of 1:2:4) in a standard TAE buffer at room temperature in the open air. In the case of Fe3O4 particle synthesis, ferric and ferrous chloride were mixed with DNA in DI water at a molar ratio of DNA/Fe2+/Fe3+ = 1:4:8 and the particles were formed via reductive precipitation, induced by increasing pH to ∼11 with addition of ammonium hydroxide. These nanocrystals are highly stable and water-soluble immediately after the synthesis, due to DNA termination. We examined the surface chemistry between oligonucleotides and nanocrystals using FTIR spectroscopy, and found that the different chemical moieties of nucleobases passivate the particle surface. Strong coordination of primary amine and carbonyl groups provides the chemical and colloidal stabilities, leading to high particle yields (Figure 1). The resulting PbS nanocrystals have a distribution of 3–6 nm in diameter, while a broader size distribution is observed with Fe3O4 nanoparticles as shown in Figure 1b and c, respectively. A similar observation was reported with the pH change-induced Fe3O4 particles of a bimodal size distribution where superparamagnetic and ferrimagnetic magnetites co-exist. In spite of the differences, FTIR measurements suggest that the chemical nature of the oligonucleotide stabilization in this case is identical to the PbS system. As a particular application, we demonstrate that aptamer-capped PbS QD can detect a target protein based on selective charge transfer, since the oligonucleotide-templated synthesis can also serve the additional purpose of providing selective binding to a molecular target. Here, we use thrombin and a thrombin-binding aptamer as a model system. These QD have diameters of 3∼6 nm and fluoresce around 1050 nm. We find that a DNA aptamer can passivate near IR fluorescent PbS nanocrystals, rendering them water-soluble and stable against aggregation, and retain the secondary conformation needed to selectively bind to its target, thrombin, as shown in Figure 2. Importantly, we find that when the aptamer-functionalized nanoparticles binds to its target (only the target), there is a highly systematic and selective quenching of the PL, even in high concentrations of interfering proteins as shown in Figure 3a and b. Thrombin is detected within one minute with a detection limit of ∼1 nM. This PL quenching is attributed to charge transfer from functional groups on the protein to the nanocrystals. A charge transfer can suppress optical transition mechanisms as we observe a significant decrease in QD absorption with target addition (Figure 3c). Here, we rule out other possibilities including Forster resonance energy transfer (FRET) and particle aggregation, because thrombin absorb only in the UV, and we did not observe any significant change in the diffusion coefficient of the particles with the target analyte, respectively. The charge transfer-induced photobleaching of QD and carbon nanotubes was observed with amine groups, Ru-based complexes, and azobenzene compounds. This selective detection of an unlabeled protein is distinct from previously reported schemes utilizing electrochemistry, absorption, and FRET. In this scheme, the target detection by a unique, direct PL transduction is observed even in the presence of high background concentrations of interfering negatively or positively charged proteins. This mechanism is the first to selectively modulate the QD PL directly, enabling new types of label free assays and detection schemes. This direct optical transduction is possible due to oligonucleotidetemplated surface passivation and molecular recognition. This chemistry may lead to more nanoparticle-based optical and magnetic probes that can be activated in a highly chemoselective manner.