Dark-Field Microscopic Study of Cellular Uptake of Carbon Nanodots: Nuclear Penetrability.

Carbon nanodots are fascinating candidates for the field of biomedicine, in applications such as bioimaging and drug delivery. However, the nuclear penetrability and process are rarely studied and lack understanding, which limits their applications for drug carriers, single-molecule detection and live cell imaging. In this study, we attempt to examine the uptake of CNDs in cells with a focus on the potential nuclear penetrability using enhanced dark-field microscopy (EDFM) associated with hyperspectral imaging (HSI) to quantitatively determine the light scattering signals of CNDs in the cells. The effects of both CND incubation time and concentration are investigated, and plausible nuclear penetration involving the nuclear pore complex (NPC) is discussed. The experimental results and an analytical model demonstrate that the CNDs' uptake proceeds by a concentration-dependent three-stage behavior and saturates at a CND incubation concentration larger than 750 µg/mL, with a half-saturated concentration of 479 µg/mL. These findings would potentially help the development of CNDs' utilization in drug carriers, live cell imaging and other biomedical applications.

Tuning the Functional Groups on Carbon Nanodots and Antioxidant Studies.

Carbon nanodots (CNDs) have shown good antioxidant capabilities by scavenging oxidant free radicals such as diphenyl-1-picrylhydrazyl radical (DPPH•) and reactive oxygen species. While some studies suggest that the antioxidation activities associate to the proton donor role of surface active groups like carboxyl groups (⁻COOH), it is unclear how exactly the extent of oxidant scavenging potential and its related mechanisms are influenced by functional groups on CNDs' surfaces. In this work, carboxyl and the amino functional groups on CNDs' surfaces are modified to investigate the individual influence of intermolecular interactions with DPPH• free radical by UV-Vis spectroscopy and electrochemistry. The results suggest that both the carboxyl and the amino groups contribute to the antioxidation activity of CNDs through either a direct or indirect hydrogen atom transfer reaction with DPPH•.

A fluorescence-electrochemical study of carbon nanodots (CNDs) in bio- and photoelectronic applications and energy gap investigation.

Carbon nanodots (CNDs) have attracted great attention due to their superior solubility, biocompatibility, tunable photoluminescence, and opto-electronic properties. This work describes a new fluorescence-based spectroelectrochemistry approach to simultaneously study the photoluminescence and wavelength dependent photocurrent of microwave synthesized CNDs. The fluorescence of CNDs shows selective quenching upon a reversible redox couple, ferricyanide/ferrocyanide, reaction during cyclic voltammetry. The CND modified gold slide electrode demonstrates wavelength dependent photocurrent generation during the fluorescence-electrochemical study, suggesting the potential application of CNDs in photoelectronics. UV-Vis absorption and electrochemistry are used to quantify the energy gap of the CNDs, and then to calibrate a Hückel model for CNDs' electronic energy levels. The Hückel (or tight binding) model treatment of an individual CND as a molecule combines the conjugated π states (C[double bond, length as m-dash]C) with the functional groups (C[double bond, length as m-dash]O, C-O, and COOH) associated with the surface electronic states. This experimental and theoretical investigation of CNDs provides a new perspective on the optoelectronic properties of CNDs and should aid in their development for practical use in biomedicine, chemical sensing, and photoelectric devices.

X-Ray absorption spectroscopy of LiBF4 in propylene carbonate: a model lithium ion battery electrolyte.

Since their introduction into the commercial marketplace in 1991, lithium ion batteries have become increasingly ubiquitous in portable technology. Nevertheless, improvements to existing battery technology are necessary to expand their utility for larger-scale applications, such as electric vehicles. Advances may be realized from improvements to the liquid electrolyte; however, current understanding of the liquid structure and properties remains incomplete. X-ray absorption spectroscopy of solutions of LiBF4 in propylene carbonate (PC), interpreted using first-principles electronic structure calculations within the eXcited electron and Core Hole (XCH) approximation, yields new insight into the solvation structure of the Li(+) ion in this model electrolyte. By generating linear combinations of the computed spectra of Li(+)-associating and free PC molecules and comparing to the experimental spectrum, we find a Li(+)-solvent interaction number of 4.5. This result suggests that computational models of lithium ion battery electrolytes should move beyond tetrahedral coordination structures.

Electrokinetic detection for X-ray spectra of weakly interacting liquids: n-decane and n-nonane.

The introduction of liquid microjets into soft X-ray absorption spectroscopy enabled the windowless study of liquids by this powerful atom-selective high vacuum methodology. However, weakly interacting liquids produce large vapor backgrounds that strongly perturb the liquid signal. Consequently, solvents (e.g., hydrocarbons, ethers, ketones, etc.) and solutions of central importance in chemistry and biology have been inaccessible by this technology. Here we describe a new detection method, upstream detection, which greatly reduces the vapor phase contribution to the X-ray absorption signal while retaining important advantages of liquid microjet sample introduction (e.g., minimal radiation damage). The effectiveness of the upstream detection method is demonstrated in this first study of room temperature liquid hydrocarbons: n-nonane and n-decane. Good agreement with first principles' calculations indicates that the eXcited electron and Core Hole theory adequately describes the subtle interactions in these liquids that perturb the electronic structure of the unoccupied states probed in core-level experiments.

STUDY OF THE NEAR INFRARED-MEDIATED HEATING OF DISPERSIONS OF PROTEIN-COATED PRISTINE AND CARBOXYLATED SINGLE-WALLED CARBON NANOTUBES.

Previously, we demonstrated the selective NIR-mediated ablation of tumor cells in vitro using pristine single-walled carbon nanotubes (SWNTs) with adsorbed tumor-targeting ligands and carboxylated SWNTs with covalently-attached ligands. The covalent approach is advantageous in ensuring that protein ligands remain associated with the NIR-absorbing SWNTs in biological matrices and the noncovalent approach has the advantage of enabling SWNT functionalization without perturbation of the SWNT lattice and photothermal properties. Herein, we compare the ability of moderately-carboxylated (~4 at.% carboxylic acid groups) and pristine SWNT materials to absorb 808 nm radiation and convert it to heat. Under conditions of a constant 808 nm laser power density, the approach involved measuring the temperature of aqueous dispersions of protein-coated SWNTs as a function of the irradiation time. Nearly identical temperature profiles were observed for dispersions of moderately-carboxylated and pristine SWNTs possessing matched 808 nm optical densities and equivalent concentrations of carbonaceous species (i.e., SWNTs and amorphous carbon impurities). The results indicate that the amount of carbonaceous species in purified dispersions of protein-coated SWNTs is more important for converting absorbed 808 nm radiation into heat than whether or not the SWNTs were moderately carboxylated, and that moderately-carboxylated SWNTs could be the SWNT-material of choice for the targeted photothermal ablation of tumor cells.

Antiproliferative and ROS Regulation Activity of Photoluminescent Curcumin-Derived Nanodots.

Recently, various types of nanomaterials have been employed to design delivery vehicles for curcumin to address the problems of poor bioavailability, low aqueous solubility, and rapid metabolism. The present study focuses on a direct one-pot synthesis of curcumin-derived nanoparticles and exploits their potential therapeutic properties in cancer cells in vitro without additional delivery vehicles. The nanoparticles, named E-Curc-dots, are synthesized using three precursor molecules, ethylenediamine (EDA), curcumin, and citric acid. The structure, composition, and physichemical properties of the nanodots are characterized and identified by employing spectroscopic and microscopic techniques. The as-synthesized E-Curc-dots exhibit bright blue photoluminescence due to the incorporation of nitrogen from the EDA precursor molecule. The characterization studies show a uniform distribution of dots with an average size of 4.6 ± 1.7 nm and, notably, that the dots retain some of the major characteristics of native curcumin with much improved water solubility and bioavailability. The E-Curc-dots show antioxidation activity at low concentrations (<0.08 mg/mL) with low levels of reactive oxygen species (ROS) generation, i.e., 82% of the ROS level in cells without treatment for A549 cells; however, at high concentrations, the nanodots exhibit a pro-oxidant effect on both the cancer cells (A549) and normal cells (EA.hy926) by inducing more ROS generation and dose-dependent cytotoxicity. The E-Curc-dots demonstrate higher cytotoxicity toward cancer cells compared to native curcumin at a lower concentration. The results indicate the efficacy of E-Curc-dots as an antiproliferative and ROS regulator with the ability of cellular bioimaging.

Novel microwave synthesis of near-metallic copper sulfide nanodiscs with size control: experimental and DFT studies of charge carrier density.

A simple unprecedented microwave synthesis of size controllable copper sufide (CuS) nanodiscs is reported. The experimental results and density functional theory (DFT)-calculated results show charge carrier densities on the order of 1021 cm-3 with an effective mass of 0.3m e, resulting in near-metallic properties.

Design of Curcumin Loaded Carbon Nanodots Delivery System: Enhanced Bioavailability, Release Kinetics, and Anticancer Activity.

Despite the potential health benefits of curcumin, such as antioxidant, anticancer, anti-inflammatory, and antimicrobial properties, its usage is limited by poor bioavailability and low aqueous solubility. Nano-formulations of curcumin have gained a lot of attention due to their increased bioavailability, solubility, circulation times, targeted specificity, decreased biodegradation, better stability, and improved cellular uptake. The current study aimed to enhance the bioavailability of curcumin using carbon nanodots (CNDs) as loading vehicles to deliver curcumin due to their excellent biocompatibility, aqueous solubility, and photoluminescence properties. Two types of CNDs (E-CNDs and U-CNDs) were used for curcumin loading and characterized for particle size, morphology, loading capability (measured as adsorption efficiency and loading capacity), stability, photoluminescence properties, in vitro drug release studies, cellular uptake, and anticancer activity. The prepared curcumin-loading CNDs (Curc-CNDs) displayed sizes around or below 10 nm with good stability. The Curc-E-CNDs demonstrated a curcumin adsorption efficiency of 91% in solution, while the Curc-U-CNDs have an adsorption efficiency of 82%. Both have a loading capacity of 3.4-3.8% with respect to the weight of the CNDs. Curcumin release followed a controlled sustained pattern that a total of 60% and 74% of curcumin was released at 72 h from Curc-E-CNDs and Curc-U-CNDs, respectively, in pH 5 buffer, and almost 90% was released in culture media within 96 h. Both of the Curc-CNDs were uptaken by cells and exhibited prominent cytotoxicity toward cancer cells. The results clearly depict the role of CNDs as efficient carriers for curcumin delivery with prolonged release and enhanced bioavailability, thereby improving the overall antitumor activity.

High Quantum Yield Fluorescent Carbon Nanodots for detection of Fe (III) Ions and Electrochemical Study of Quenching Mechanism.

Carbon nanodots (CNDs) offer potential applications in photocatalysis, optoelectronics, bio-imaging, and sensing due to their excellent photoluminescence (PL) properties, biocompatibility, aqueous solubility, and easy functionalization. Recent emphasis on CNDs in the selective detection of metal ions is due to the growing concern for human and environmental safety. In this work, two types of fluorescent carbon nanodots (CNDs) are synthesized economically from ethylene diamine (E-CNDs) or urea (U-CNDs) in a single step microwave process. The as-prepared CNDs exhibit excellent PL at an excitation wavelength of 350 nm with a quantum yield of 64% for E-CNDs and 8.4% for U-CNDs with reference to quinine sulfate. Both E-CNDs and U-CNDs demonstrate high selectivity towards Fe (III) ions among different metal ions, by fluorescence quenching in a dose dependent manner. The limit of detection of E-CNDs and U-CNDs is observed to be 18 nM and 30 nM, respectively, in the linear response range of 0-2000 µM with a short response time (seconds). The CNDs detect Fe (III) ions in tap water and serum sample with no spiking and the recovery was ~100% with the Fe (III) samples. Cellular internalization studies confirm the localization of the CNDs and the optical imaging sensing of Fe (III) ions inside living cells. A charge transfer fluorescence quenching mechanism, specifically between the CNDs and Fe (III), is proposed and examined using cyclic voltammetry. The overall characteristics of the E-CNDs provides a potential sensing platform in highly sensitive and selective detection of Fe (III) ions.

Antioxidant Capacity of Nitrogen and Sulfur Codoped Carbon Nanodots.

Carbon nanodots (CNDs) have shown potential for antioxidative activity at the cellular level. Here we applied a facile hydrothermal method to prepare fluorescent nitrogen and sulfur (N,S-)codoped CNDs using α-lipoic acid, citric acid, and urea as precursor molecules. This work describes a comprehensive study for exploring their antioxidation activity using UV-vis absorption and electrochemistry measurements of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), as well as a lucigenin chemiluminescence (lucigenin-CL) assay. The lucigenin-CL assay detects superoxide anion radicals, i.e., reactive oxygen species (ROS) produced through the xanthine/xanthine oxidase (XO) reaction. The electrochemically derived relationship between the unreacted nitrogen-centered DPPH• and CND concentrations agrees with that obtained from UV-vis measurements. A reaction pathway for the ROS antioxidative reaction of N,S-codoped CNDs is proposed. These findings should aid in the development of N,S-codoped CNDs for practical use in biomedical applications.