Strategies for Incorporating Graphene Oxides and Quantum Dots into Photoresponsive Azobenzenes for Photonics and Thermal Applications.

Graphene represents a new generation of materials which exhibit unique physicochemical properties such as high electron mobility, tunable optics, a large surface to volume ratio, and robust mechanical strength. These properties make graphene an ideal candidate for various optoelectronic, photonics, and sensing applications. In recent years, numerous efforts have been focused on azobenzene polymers (AZO-polymers) as photochromic molecular switches and thermal sensors because of their light-induced conformations and surface-relief structures. However, these polymers often exhibit drawbacks such as low photon storage lifetime and energy density. Additionally, AZO-polymers tend to aggregate even at moderate doping levels, which is detrimental to their optical response. These issues can be alleviated by incorporating graphene derivatives (GDs) into AZO-polymers to form orderly arranged molecules. GDs such as graphene oxide (GO), reduced graphene oxide (RGO), and graphene quantum dots (GQDs) can modulate the optical response, energy density, and photon storage capacity of these composites. Moreover, they have the potential to prevent aggregation and increase the mechanical strength of the azobenzene complexes. This review article summarizes and assesses literature on various strategies that may be used to incorporate GDs into azobenzene complexes. The review begins with a detailed analysis of structures and properties of GDs and azobenzene complexes. Then, important aspects of GD-azobenzene composites are discussed, including: (1) synthesis methods for GD-azobenzene composites, (2) structure and physicochemical properties of GD-azobenzene composites, (3) characterization techniques employed to analyze GD-azobenzene composites, and most importantly, (4) applications of these composites in various photonics and thermal devices. Finally, a conclusion and future scope are given to discuss remaining challenges facing GD-azobenzene composites in functional science engineering.

Assessing Advantages and Drawbacks of Rapidly Generated Ultra-Large 3D Breast Cancer Spheroids: Studies with Chemotherapeutics and Nanoparticles.

Traditionally, two-dimensional (2D) monolayer cell culture models have been used to study in vitro conditions for their ease of use, simplicity and low cost. However, recently, three-dimensional (3D) cell culture models have been heavily investigated as they provide better physiological relevance for studying various disease behaviors, cellular activity and pharmaceutical interactions. Typically, small-sized tumor spheroid models (100-500 µm) are used to study various biological and physicochemical activities. Larger, millimetric spheroid models are becoming more desirable for simulating native tumor microenvironments (TMEs). Here, we assess the use of ultra-large spheroid models (~2000 µm) generated from scaffolds made from a nozzle-free, ultra-high resolution printer; these models are explored for assessing chemotherapeutic responses with molecular doxorubicin (DOX) and two analogues of DoxilⓇ (Dox-NPⓇ, DoxovesTM) on MDA-MB-231 and MCF-7 breast cancer cell lines. To provide a comparative baseline, small spheroid models (~500 µm) were developed using a self-aggregation method of MCF-7 breast cancer cell lines, and underwent similar drug treatments. Analysis of both large and small MCF-7 spheroids revealed that Dox-NP tends to have the highest level of inhibition, followed by molecular doxorubicin and then Doxoves. The experimental advantages and drawbacks of using these types of ultra-large spheroids for cancer research are discussed.

Data on thermal conductivity and dynamic mechanical properties of graphene quantum dots in epoxy.

Graphene Quantum Dots (GQDs) and epoxy have been combined into a nanocomposite and evaluated for their thermal and dynamic mechanical properties. Samples of varying GQD mass loading were first examined with SEM in several images. Thermal conductivity was estimated using Differential Scanning Calorimetry (DSC) with a step analysis technique and analysis program. Several dynamic mechanical properties were recorded using Dynamic Mechanical Analysis (DMA) and displayed in their raw and analyzed formats. For more insight please see Infusion of graphene quantum dots to modulate thermal conductivity and dynamic mechanical properties of polymers [1].

Carbon-based artificial SEI layers for aqueous lithium-ion battery anodes.

Replacing flammable organic electrolytes with aqueous electrolytes in lithium-ion batteries (LIB) can greatly enhance the safety of next-generation energy storage systems. With the extended electrochemical stability window of electrolytes, 'water-in-salt' (WIS) electrolytes containing LIB presented significant performance improvements. However, the solubility limits of lithium salts in water restrain the extent of kinetic protection offered by the high salt concentration. Here, we report design strategies of anode structure to improve the cycle life of LIB with WIS electrolytes. We introduced partially graphitic protective carbon layers on anode particles using a versatile coating method. This protective layer not only improved charge transfer kinetics but also minimized the exposure of anode surface for water electrolysis. The effectiveness of anode structure developed in this study was exemplified on TiO2 anodes, where cycle performance and coulombic efficiency improved by 11 times and 29% respectively over the base anode material.

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles.

Nanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

Herringbone-Patterned 3D-Printed Devices as Alternatives to Microfluidics for Reproducible Production of Lipid Polymer Hybrid Nanoparticles.

Major barriers to the implementation of nanotechnology include reproducible synthesis and scalability. Batch solution phase methods do not appear to have the potential to overcome these barriers. Microfluidic methods have been investigated as a means to enable controllable and reproducible synthesis; however, the most popular constituent of microfluidics, polydimethylsiloxane, is ill-suited for mass production. Multi-inlet vortex mixers (MIVMs) have been proposed as a method for scalable nanoparticle production; however, the control and reproducibility of the nanoparticle is wanting. Here, we investigate the ability to improve the control and reproducibility of nanoparticles produced by using 3D printed MIVMs with herringbone patterns in the flow channels. We compare three methods, viz., microfluidic, MIVM, and herringbone-patterned MIVM methods, for the synthesis of lipid-polymer hybrid nanoparticles (LPHNPs). The 3D printed herringbone-patterned MIVM method resulted in the smallest LPHNPs with the most uniform size distribution and shows more reproducible results as compared to the other two methods. To elucidate the mechanism underlying these results, concentration slices and vorticity streamlines of mixing chambers have been analyzed for 3D printed herringbone-patterned MIVM devices. The results bode well for LPHNPs, a formulation widely investigated for its improved therapeutic efficacy and biocompatibility. The herringbone-patterned device also has the potential to be broadly applied to many solution phase processes that take advantage of efficient mixing. The methods discussed here have broad implications for reproducible production of nanoparticles with constituents such as siRNA, proteins, quantum dots, and inorganic materials.

Infusion of Graphene Quantum Dots to Create Stronger, Tougher, and Brighter Polymer Composites.

Incorporation of nanoparticles into polymer resins has recently attracted a significant amount of attention from researchers for the nanoparticles' ability to alter the properties of the resin. Whereas graphene-based structures possess a two-dimensional honeycomb arrangement of carbon atoms that makes them desirable for engineering composite materials, quantum dot formulations have been primarily used in optoelectronic applications that take advantage of quantum confinement and size-tunable properties. Graphene and quantum dots (GQDs) are ubiquitous in the current research literature; however, the impact of GQD on the physical properties of polymer resins like epoxy remains unclear. Here, we show that infusing GQD into an epoxy polymer matrix results in (1) a 2.6-fold increase in the toughness of the polymer resins, (2) a 2.25-fold increase in the tensile strength of the polymer resins compared to its original tensile strength, (3) uniform loading at weight percentages as high as 10% of the polymer resin, (4) an 18% change to the max % increase in tensile strain compared to that of the neat polymer resin without GQDs, even though there is an increase in tensile strength, and (5) a 2.5-times increase in Young's modulus compared to that of the neat polymer resin, all while maintaining excellent optical properties of the composite formulation. Our results demonstrate that GQDs with dual acid and alcohol functional groups can enable high loading percentages, which, in turn, give rise to composite materials that are simultaneously stronger and tougher. We believe that these GQDs, created from an abundant source, are a starting point for new and more sophisticated composite materials with potential in mechanical, electrical, and photosensitive applications.

Bioengineering silicon quantum dot theranostics using a network analysis of metabolomic and proteomic data in cardiac ischemia.

Metabolomic profiling is ideally suited for the analysis of cardiac metabolism in healthy and diseased states. Here, we show that systematic discovery of biomarkers of ischemic preconditioning using metabolomics can be translated to potential nanotheranostics. Thirty-three patients underwent percutaneous coronary intervention (PCI) after myocardial infarction. Blood was sampled from catheters in the coronary sinus, aorta and femoral vein before coronary occlusion and 20 minutes after one minute of coronary occlusion. Plasma was analysed using GC-MS metabolomics and iTRAQ LC-MS/MS proteomics. Proteins and metabolites were mapped into the Metacore network database (GeneGo, MI, USA) to establish functional relevance. Expression of 13 proteins was significantly different (p<0.05) as a result of PCI. Included amongst these was CD44, a cell surface marker of reperfusion injury. Thirty-eight metabolites were identified using a targeted approach. Using PCA, 42% of their variance was accounted for by 21 metabolites. Multiple metabolic pathways and potential biomarkers of cardiac ischemia, reperfusion and preconditioning were identified. CD44, a marker of reperfusion injury, and myristic acid, a potential preconditioning agent, were incorporated into a nanotheranostic that may be useful for cardiovascular applications. Integrating biomarker discovery techniques into rationally designed nanoconstructs may lead to improvements in disease-specific diagnosis and treatment.

Assessing clinical prospects of silicon quantum dots: studies in mice and monkeys.

Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots.

On-demand hydrogen generation using nanosilicon: splitting water without light, heat, or electricity.

We demonstrate that nanosize silicon (~10 nm diameter) reacts with water to generate hydrogen 1000 times faster than bulk silicon, 100 times faster than previously reported Si structures, and 6 times faster than competing metal formulations. The H(2) production rate using 10 nm Si is 150 times that obtained using 100 nm particles, dramatically exceeding the expected effect of increased surface to volume ratio. We attribute this to a change in the etching dynamics at the nanoscale from anisotropic etching of larger silicon to effectively isotropic etching of 10 nm silicon. These results imply that nanosilicon could provide a practical approach for on-demand hydrogen production without addition of heat, light, or electrical energy.

Plasmonic gold and luminescent silicon nanoplatforms for multimode imaging of cancer cells.

The development of multimodal nanoparticle platforms is desirable for cancer nanotechnology applications. Creating single nanoplatforms with both plasmonic and photoluminescent optical properties has remained a challenge, because combining discrete entities each having one of these unique properties typically results in the attenuation of one of the desirable properties. Here, we overcome challenges associated with combining plasmonic gold with luminescent silicon nanocrystals for biological imaging applications by incorporating multiple silicon quantum dots into the core of a micelle and then depositing gold on the surface of the nanostructure. Within the newly developed nanoconstruct, the gold shell exhibits plasmonic light scattering properties useful for dark field imaging, while the silicon nanocrystals maintain their photoluminescence. The result is a nanoplatform with both plasmonic and luminescent properties in a useful form. Multimodal imaging of pancreatic cancer cells demonstrates overlap of luminescence from the silicon quantum dots with light scattering from the gold shell. This approach can be tailored to other formulations and address the challenge of fluorescence attenuation that is typically observed when quantum dots are combined with plasmonic materials. The usefulness of these particles may eventually extend beyond multimodal imaging to include photothermal treatment.

Open access integrated therapeutic and diagnostic platforms for personalized cardiovascular medicine.

It is undeniable that the increasing costs in healthcare are a concern. Although technological advancements have been made in healthcare systems, the return on investment made by governments and payers has been poor. The current model of care is unsustainable and is due for an upgrade. In developed nations, a law of diminishing returns has been noted in population health standards, whilst in the developing world, westernized chronic illnesses, such as diabetes and cardiovascular disease have become emerging problems. The reasons for these trends are complex, multifactorial and not easily reversed. Personalized medicine has the potential to have a significant impact on these issues, but for it to be truly successful, interdisciplinary mass collaboration is required. We propose here a vision for open-access advanced analytics for personalized cardiac diagnostics using imaging, electrocardiography and genomics.

Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications.

Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd³âº) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd³âº. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM⁻¹ s⁻¹ (in terms of Gd³âº concentration), calculated to be around 6000 mM⁻¹ s⁻¹ per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.

Gene Silencing of Human Neuronal Cells for Drug Addiction Therapy using Anisotropic Nanocrystals.

Theranostic platform integrating diagnostic imaging and therapeutic function into a single system has become a new direction of nanoparticle research. In the process of treatment, therapeutic efficacy is monitored. The use of theranostic nanoparticle can add an additional "layer" to keep track on the therapeutic agent such as the pharmacokinetics and biodistribution. In this report, we have developed quantum rod (QR) based formulations for the delivery of small interfering RNAs (siRNAs) to human neuronal cells. PEGlyated QRs with different surface functional groups (amine and maleimide) were designed for selectively down-regulating the dopaminergic signaling pathway which is associated with the drug abuse behavior. We have demonstrated that the DARPP-32 siRNAs were successfully delivered to dopaminergic neuronal (DAN) cells which led to drastic knockdown of specific gene expression by both the electrostatic and covalent bond conjugation regimes. The PEGlyated surface offered high biocompatibilities and negligible cytotoxicities to the QR formulations that may facilitate the in vivo applications of these nanoparticles.

Energy transfer from a dye donor to enhance the luminescence of silicon quantum dots.

Quantum dots are known for their superior optical properties; however, when transferred into aqueous media, their luminescent properties are frequently compromised. When encapsulated in micelles for bioimaging applications, luminescent silicon quantum dots can lose as much as 50% of their luminescence depending on the formulation used. Here, we create an energy transfer micelle platform that combines silicon quantum dots with an anthracene-based dye in the hydrophobic core of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) micelles. These phospholipid micelles are water dispersible, stable, and surrounded by a PEGylated layer with modifiable functional groups. The spectroscopic properties of energy transfer between the anthracene donors and silicon quantum dot acceptors were analyzed based on the observed dependence of the steady-state emission spectrum on concentration ratio, excitation wavelength, pH, and temperature. The luminescence of silicon quantum dots from the core of a 150 nm micelle is enhanced by more than 80% when the anthracene dye is added. This work provides a simple yet readily applicable solution to the long-standing problem of luminescence enhancement of silicon quantum dots and can serve as a template for improving the quantum dot emission yield for biological applications where luminescence signal enhancements are desirable and for solar applications where energy transfer plays a critical role in device performance.

Creating ligand-free silicon germanium alloy nanocrystal inks.

Particle size is widely used to tune the electronic, optical, and catalytic properties of semiconductor nanocrystals. This contrasts with bulk semiconductors, where properties are tuned based on composition, either through doping or through band gap engineering of alloys. Ideally, one would like to control both size and composition of semiconductor nanocrystals. Here, we demonstrate production of silicon-germanium alloy nanoparticles by laser pyrolysis of silane and germane. We have used FTIR, TEM, XRD, EDX, SEM, and TOF-SIMS to conclusively determine their structure and composition. Moreover, we show that upon extended sonication in selected solvents, these bare nanocrystals can be stably dispersed without ligands, thereby providing the possibility of using them as an ink to make patterned films, free of organic surfactants, for device fabrication. The engineering of these SiGe alloy inks is an important step toward the low-cost fabrication of group IV nanocrystal optoelectronic, thermoelectric, and photovoltaic devices.

Bioconjugation of luminescent silicon quantum dots for selective uptake by cancer cells.

Conventional quantum dots have great potential in cancer-related imaging and diagnostic applications; however, these applications are limited by concerns about the inherent toxicity of their core materials (e.g., cadmium, lead). Virtually all imaging applications require conjugation of the imaging agent to a biologically active molecule to achieve selective uptake or binding. Here, we report a study of biocompatible silicon quantum dots covalently attached to biomolecules including lysine, folate, antimesothelin, and transferrin. The particles possess desirable physical properties, surface chemistry, and optical properties. Folate- and antimesothelin-conjugated silicon quantum dots show selective uptake into Panc-1 cells. This study contributes to the preclinical evaluation of silicon quantum dots and further demonstrates their potential as an imaging agent for cancer applications.

Multimodal imaging probes based on Gd-DOTA conjugated quantum dot nanomicelles.

Recently, multimodal nanoparticles integrating dual- or tri-imaging modalities into a single hybrid nanosystem have attracted plenty of attention in biomedical research. Here, we report the fabrication of two types of multimodal micelle-encapsulated nanoparticles, which were systematically characterized and thoroughly evaluated in terms of their imaging potential and biocompatibility. Optical and magnetic resonance (MR) imaging probes were integrated by conjugating DOTA-gadolinium (Gd) derivative to quantum dot based nanomicelles. Two amphiphilic block copolymer micelles, amine-terminated mPEG-phospholipid and amine-modified Pluronic F127, were chosen as the capping agents because of their excellent biocompatibility and ability to prevent opsonization and prolong circulation time in vivo. Owing to their different hydrophobic-hydrophilic structure, the micellar aggregates exhibited different sizes and protection of core QDs. This work revealed the differences between these nanomicelles in terms of the stability over a wide range of pH, along with their cytotoxicity and the capacity for chelating gadolinium, thus providing a useful guideline for tailor-making multimodal nanoparticles for specific biomedical applications.

Non-invasive tumor detection in small animals using novel functional Pluronic nanomicelles conjugated with anti-mesothelin antibody.

In this study QDs were encapsulated in carboxylated PluronicF127 (F127COOH) triblock polymeric micelles and conjugated with anti-mesothelin antibody for the purpose of alleviating potential toxicity, enhancing the stability and improving targeting efficiency of CdTe/ZnS quantum dots (QDs) in tumors. The amphiphilic triblock polymer of F127COOH contains hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) units. After encapsulating QDs into carboxylated F127 (F127COOH-QD) micelles, the particles were conjugated with anti-mesothelin antibodies to allow targeting of cancerous areas. The size of the monodispersed spherical QD-containing micelles was determined to be ∼120 nm by dynamic light scattering (DLS). The critical micelle concentration (CMC) was estimated to be 4.7 × 10(-7) M. In an in vitro study, the anti-methoselin antibody conjugated F127COOH (Me-F127COOH-QD) nanomicelles showed negligible cytotoxicity to pancreatic cancer cells (Panc-1). Confocal microscopy demonstrated that the Me-F127COOH-QD nanomicelles were taken up more efficiently by Panc-1 cells, due to antibody mediated targeting. An in vivo imaging study showed that Me-F127COOH-QD nanomicelles accumulated at the pancreatic tumor site 15 min after intravenous injection. In addition, the low in vivo toxicity of the nanomicellar formulation was evaluated by pathological assays. These results suggest that anti-mesothein antibody conjugated carboxylated F127 nanomicelles may serve as a promising nanoscale platform for early human pancreatic cancer detection and targeted drug delivery.

In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals.

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.