Porous silicon-poly(ε-caprolactone) film composites: evaluation of drug release and degradation behavior.

This work focuses on an evaluation of novel composites of porous silicon (pSi) with the biocompatible polymer ε-polycaprolactone (PCL) for drug delivery and tissue engineering applications. The degradation behavior of the composites in terms of their morphology along with the effect of pSi on polymer degradation was monitored. PSi particles loaded with the drug camptothecin (CPT) were physically embedded into PCL films formed from electrospun PCL fiber sheets. PSi/PCL composites revealed a release profile of CPT (monitored via fluorescence spectroscopy) in accordance with the Higuchi release model, with significantly lower burst release percentage compared to pSi microparticles alone. Degradation studies of the composites, using gravimetric analysis, differential scanning calorimetry (DSC), and field emission scanning electron microscopy (FESEM), carried out in phosphate-buffered saline (PBS) under simulated physiological conditions, indicated a modest mass loss (15%) over 5 weeks due to pSi dissolution and minor polymer hydrolysis. DSC results showed that, relative to PCL-only controls, pSi suppressed crystallization of the polymer film during PBS exposure. This suppression affects the evolution of surface morphology during this exposure that, in turn, influences the degradation behavior of the polymer. The implications of the above properties of these composites as a possible therapeutic device are discussed.

In Vitro Gene Delivery with Large Porous Silicon Nanoparticles Fabricated Using Cost-Effective, Metal-Assisted Chemical Etching.

The cytocompatibility, cell membrane affinity, and plasmid DNA delivery from surface oxidized, metal-assisted stain-etched mesoporous silicon nanoscale particles (pSiNPs) to human embryonic kidney (HEK293) cells is demonstrated, suggesting the possibility of using such material for targeted transfection and drug delivery.

Biogenic Nanostructured Porous Silicon as a Carrier for Stabilization and Delivery of Natural Therapeutic Species.

Nanostructured mesoporous silicon (pSi) derived from the silicon-accumulator plant Tabasheer (Bambuseae) is demonstrated to serve as a potential carrier matrix for carrying and stabilizing naturally active, but otherwise metastable, therapeutic agents. Particularly, in this study, garlic oil containing phytochemicals (namely, allicin) that are capable of inhibiting Staphylococcus aureus (S. aureus) bacterial growth were incorporated into Tabasheer-derived porous silicon. Thermogravimetric analysis (TGA) indicated that relatively high amounts of the extract (53.1 ± 2.2 wt %) loaded into pSi are possible by simple infiltration. Furthermore, by assessing the antibacterial activity of the samples using a combination technique of agar disk diffusion and turbidity assays against S. aureus, we report that biogenic porous silicon can be utilized to stabilize and enhance the therapeutic effects of garlic oil for up to 4 weeks when the samples were stored under refrigerated conditions (4 °C) and 1 week at room temperature (25 °C). Critically, under ultraviolet (UV) light (365 nm) irradiation for 24 h intervals, plant-derived pSi is shown to have superior performance in protecting garlic extracts over porous silica (pSiO2) derived from the same plant feedstock or extract-only controls. The mechanism for this effect has also been investigated.

Control of CH3 NH3 PbI3 Perovskite Nanostructure Formation through the Use of Silicon Nanotube Templates.

A new route to formation of methylammonium lead iodide perovskite nanostructures is reported whose dimensions are controlled by the use of porous silicon nanotube templates. Optical absorption and photoluminescence properties for perovskite nanostructures of 70 and 200 nm in width are evaluated, along with comparisons with larger 1D microwires of the same composition.

Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers.

The synthesis and solubility behaviors of four generation five (G5) triazine dendrimers are studied. While the underivatized cationic dendrimer is soluble in water, the acetylated and propanoylated derivatives undergo coacervation in water upon increasing temperature. Occurring around room temperature, this behavior is related to a liquid-liquid phase transition with a lower critical solution temperature (LCST) and is explained by differences in composition, notably, the hydrophobic nature of the terminal groups. Interestingly, the water solubility of the acetylated dendrimer is affected by the addition of selected metal ions. Titrating solutions of acetylated dendrimer at temperatures below the LCST with gold or palladium ions promoted precipitation, but platinum, iridium, and copper did not. Gold nanoparticles having diameters of 2.5 ± 0.8 nm can be obtained from solutions of the acetylated dendrimer at concentrations of gold less than that required to induce precipitation by treating the solution with sodium borohydride.

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye.

Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 µm or <40 µm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi-PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells.

Influence of Surface Chemistry on the Release of an Antibacterial Drug from Nanostructured Porous Silicon.

Nanostructured mesoporous silicon possesses important properties advantageous to drug loading and delivery. For controlled release of the antibacterial drug triclosan, and its associated activity versus Staphylococcus aureus, previous studies investigated the influence of porosity of the silicon matrix. In this work, we focus on the complementary issue of the influence of surface chemistry on such properties, with particular regard to drug loading and release kinetics that can be ideally adjusted by surface modification. Comparison between drug release from as-anodized, hydride-terminated hydrophobic porous silicon and the oxidized hydrophilic counterpart is complicated due to the rapid bioresorption of the former; hence, a hydrophobic interface with long-term biostability is desired, such as can be provided by a relatively long chain octyl moiety. To minimize possible thermal degradation of the surfaces or drug activity during loading of molten drug species, a solution loading method has been investigated. Such studies demonstrate that the ability of porous silicon to act as an effective carrier for sustained delivery of antibacterial agents can be sensitively altered by surface functionalization.

Cancer Therapeutic siRNA Delivery and Imaging by Nitrogen- and Neodymium-Doped Graphene Quantum Dots.

While small interfering RNA (siRNA) technology has become a powerful tool that can enable cancer-specific gene therapy, its translation to the clinic is still hampered by the inability of the genes alone to cell transfection, poor siRNA stability in blood, and the lack of delivery tracking capabilities. Recently, graphene quantum dots (GQDs) have emerged as a novel platform allowing targeted drug delivery and fluorescence image tracking in visible and near-infrared regions. These capabilities can aid in overcoming primary obstacles to siRNA therapeutics. Here, for the first time, we utilize biocompatible nitrogen- and neodymium-doped graphene quantum dots (NGQDs and Nd-NGQDs, respectively) for the delivery of Kirsten rat sarcoma virus (KRAS) and epidermal growth factor receptor (EGFR) siRNA effective against a variety of cancer types. GQDs loaded with siRNA noncovalently facilitate successful siRNA transfection into HeLa cells, confirmed by confocal fluorescence microscopy at biocompatible GQD concentrations of 375 µg/mL. While the GQD platform provides visible fluorescence tracking, Nd doping enables deeper-tissue near-infrared fluorescence imaging suitable for both in vitro and in vivo applications. The therapeutic efficacy of the GQD/siRNA complex is verified by successful protein knockdown in HeLa cells at nanomolar siEGFR and siKRAS concentrations. A range of GQD/siRNA loading ratios and payloads are tested to ultimately provide substantial inhibition of protein expression down to 31-45%, comparable with conventional Lipofectamine-mediated delivery. This demonstrates the promising potential of GQDs for the nontoxic delivery of siRNA and genes in general, complemented by multiwavelength image tracking.

Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness.

Reconstituted high-density lipoprotein nanoparticles (rHDL NPs) have been utilized as delivery vehicles to a variety of targets, including cancer cells. However, the modification of rHDL NPs for the targeting of the pro-tumoral tumor-associated macrophages (TAMs) remains largely unexplored. The presence of mannose on nanoparticles can facilitate the targeting of TAMs which highly express the mannose receptor at their surface. Here, we optimized and characterized mannose-coated rHDL NPs loaded with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an immunomodulatory drug. Lipids, recombinant apolipoprotein A-I, DMXAA, and different amounts of DSPE-PEG-mannose (DPM) were combined to assemble rHDL-DPM-DMXAA NPs. The introduction of DPM in the nanoparticle assembly altered the particle size, zeta potential, elution pattern, and DMXAA entrapment efficiency of the rHDL NPs. Collectively, the changes in physicochemical characteristics of rHDL NPs upon the addition of the mannose moiety DPM indicated that the rHDL-DPM-DMXAA NPs were successfully assembled. The rHDL-DPM-DMXAA NPs induced an immunostimulatory phenotype in macrophages pre-exposed to cancer cell-conditioned media. Furthermore, rHDL-DPM NPs delivered their payload more readily to macrophages than cancer cells. Considering the effects of the rHDL-DPM-DMXAA NPs on macrophages, the rHDL-DPM NPs have the potential to serve as a drug delivery platform for the selective targeting of TAMs.

Encapsulated MAPbBr3 in nickel oxide nanotubes and their electroluminescence.

Metal halide perovskites have emerged as the next generation of light emitting semiconducting materials due to their excellent properties such as tunable bandgaps, high photoluminescence quantum yield, and high color purity. Nickel oxide is a hole transport material that has been used in planar light emitting diodes (LEDs). In this paper, we develop a novel method for the large scale fabrication of metal halide perovskite nanowire arrays encapsulated inside nickel oxide nanotubes. We study the structural and spectral properties of these infiltrated perovskites nanowires and, to the best of our knowledge, for the first time report on a working LED device consisting of perovskites encapsulated inside nickel oxide nanotubes. Finally, we study the photoluminescence and electroluminescence of an LED with MAPbBr3 inside nickel oxide nanotubes and obtain an outstanding current efficiency of 5.99 Cd A-1 and external quantum efficiency of 3.9% for the LED device.

Nanoporous Silicon as a Green, High-Tech Educational Tool.

Pedagogical tools are needed that link multidisciplinary nanoscience and technology (NST) to multiple state-of-the-art applications, including those requiring new fabrication routes relying on green synthesis. These can both educate and motivate the next generation of entrepreneurial NST scientists to create innovative products whilst protecting the environment and resources. Nanoporous silicon shows promise as such a tool as it can be fabricated from plants and waste materials, but also embodies many key educational concepts and key industrial uses identified for NST. Specific mechanical, thermal, and optical properties become highly tunable through nanoporosity. We also describe exceptional properties for nanostructured silicon like medical biodegradability and efficient light emission that open up new functionality for this semiconductor. Examples of prior lecture courses and potential laboratory projects are provided, based on the author's experiences in academic chemistry and physics departments in the USA and UK, together with industrial R&D in the medical, food, and consumer-care sectors. Nanoporous silicon-based lessons that engage students in the basics of entrepreneurship can also readily be identified, including idea generation, intellectual property, and clinical translation of nanomaterial products.

Morphology-dependent fluorescence of europium-doped cerium oxide nanomaterials.

Europium-doped CeO2 nanomaterials have been investigated for a variety of sensing and biological applications, as doping enhances the catalytic activity of CeO2 and contributes visible fluorescence to the nanomaterial. However, scant evidence is available that directly compares Eu3+ fluorescence from multiple morphologies establishing useful correlation(s) between physical and optical trends in such structures. To address this shortcoming, Eu3+-doped CeO2 nanorods, nanowires, nanocubes, and annealed nanorods were synthesized and characterized, representing a range of crystalline defect sizes, defect concentrations, and surface moieties. Morphologies rich with oxygen defects and hydroxyl groups (assessed via X-ray photoelectron spectroscopy) quenched the Eu3+ fluorescence, while samples with larger crystalline domains and lower Ce3+ concentrations have relatively stronger emission intensities. Of the four morphologies, nanocubes exhibit the strongest emission, as each structure is monocrystalline with few oxygen defects and associated quenching sites. Furthermore, the Eu3+ hypersensitive transition is more responsive to the dopant concentration in the nanocubes, as defects induced by the dopant are not removed by thermal annealing.

Sustained antibacterial activity from triclosan-loaded nanostructured mesoporous silicon.

In this work, nanostructured particles of porous silicon are demonstrated to act as an effective carrier for the sustained delivery of antibacterial agents with an enhanced inhibitory activity. Methods are described for the incorporation of significant amounts of the established antibacterial compound triclosan (Irgasan) into mesoporous silicon of varying porosities. Such materials were characterized by a combination of scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), and antimicrobial assays. Assessment of antibacterial activity was carried out versus the bacterium Staphylococcus aureus as a function of time with concomitant assessment of triclosan release; significant, sustained inhibition of bacterial growth is demonstrated in the triclosan-containing porous Si for time intervals greater than 100 days. Significantly, enhanced dissolution (relative to room temperature equilibrium solubility) of the triclosan was observed for the initial 15 days of drug release, inferring some amorphization or nanostructuring by the porous Si matrix.

Formation of Platinum Nanocrystals on Silicon Nanotubes and Corresponding Anti-Cancer Activity in Vitro.

Biodegradable porous silicon nanotubes (pSiNTs), functionalized with primary amine moieties via the use of 3-aminopropyltriethoxysilane (APTES), is demonstrated as a template for formation of platinum nanocrystals (Pt NCs) (1-3 nm). Transmission electron microscopy-energy dispersive X-ray analysis (TEM-EDX) indicates a relatively high and tunable concentration of Pt uniformly immobilized on a given nanotube (wt % Pt: 20-60%). In vitro viability and cellular uptake studies are consistent with a time-dependent toxicity of Pt NCs-pSiNTs against HeLa cells that is influenced by the degradation kinetics of the pSiNTs; internalization of the composites inside the cells exerts cellular damage in an apoptotic manner, therefore suggesting promising future applications in anticancer treatments.

Rare-Earth-Doped Cerium Oxide Nanocubes for Biomedical Near-Infrared and Magnetic Resonance Imaging.

Near-infrared (NIR) fluorescence provides a new avenue for biomedical fluorescence imaging that allows for the tracking of fluorophore through several centimeters of biological tissue. However, such fluorophores are rare and, due to accumulation-derived toxicity, are often restricted from clinical applications. Deep tissue imaging not only provided by near-infrared fluorophores but also conventionally carried out by magnetic resonance imaging (MRI) or computed tomography (CT) is also hampered by the toxicity of the contrast agents. This work offers a biocompatible imaging solution: cerium oxide (CeO2) nanocubes doped with ytterbium or neodymium, and co-doped with gadolinium, showing simultaneous potential for near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) applications. A synthetic process described in this work allows for the stable incorporation of ytterbium or neodymium, both possessing emissive transitions in the NIR. As a biocompatible nanomaterial, the CeO2 nanocubes act as an ideal host material for doping, minimizing lanthanide fluorescence self-quenching as well as any potential toxicity associated with the dopants. The uptake of nanocubes by HeLa cells maximized at 12 h was monitored by hyperspectral imaging of the ytterbium or neodymium NIR emission, indicating the capacity of the lanthanide-doped nanocubes for in vitro and a potential for in vivo fluorescence imaging. The co-doped nanocubes demonstrate no significant loss of NIR emission intensity upon co-doping with 2 atomic % gadolinium and exhibit magnetic susceptibilities in the range of known negative contrast agents. However, a small increase to 6 atomic % gadolinium significantly affects the magnetic susceptibility ratio (r2/r1), shifting closer to the positive contrast range and suggesting the potential use of the CeO2 nanocube matrix doped with selected rare-earth ions as a tunable MRI contrast agent with NIR imaging capabilities.

Structural and spectroscopic studies of a nanostructured silicon-perovskite interface.

While extensively investigated in thin film form for energy materials applications, this work investigates the formation of APbBr3 structures (A = CH3NH3+ (MA), Cs+) in silicon and oxidized silicon nanotubes (SiNTs) with varying inner diameter. We carefully control the extent of oxidation of the nanotube host and correlate the relative Si/Si oxide content in a given nanotube host with the photoluminescence quantum efficiency (PLQE) of the perovskite. Complementing these measurements is an evaluation of average PL lifetimes of a given APbBr3 nanostructure, as evaluated by time-resolved confocal photoluminescence measurements. Increasing Si (decreasing oxide) content in the nanotube host results in a sensitive reduction of MAPbBr3 PLQE, with a concomitant decrease in average lifetime (τave). We interpret these observations in terms of decreased defect passivation by a lower concentration of oxide species surrounding the perovskite. In addition, we show that the use of selected nanotube templates leads to more stable perovskite PL in air over time (weeks). Taken in concert, such fundamental observations have implications for interfacial carrier interactions in tandem Si/perovskite photovoltaics.

Silicon Nanotubes as Potential Therapeutic Platforms.

Silicon nanotubes (SiNTs) with unique well-defined structural morphologies have been successfully fabricated and recognized as a novel architecture in the nanoscale Si family. While the typical dendritic microstructure of mesoporous silicon prepared anodically has been exploited previously for therapeutics and biosensing, our status of utilizing SiNTs in this regard is still in its infancy. In this review, we focus on the fundamental properties of such nanotubes relevant to therapeutic applications, beginning with a description of our ability to sensitively tune the structure of a given SiNT through synthetic control and the associated detailed in vitro dissolution behavior (reflecting biodegradability). Emphasis is also placed here on the range of functional moieties available to attach to the surface of SiNTs through a summary of current studies involving surface functionalization and strategies that facilitate conjugation with molecules of interest for multiple purposes, including cell labeling, nucleotide attachment, and scaffolding of therapeutic metallic nanoparticles. Experiments addressing our ability to load the interior of a given nanotube with species capable of providing magnetic field-assisted drug delivery are also briefly described. Given the range of diverse properties demonstrated to date, we believe the future to be quite promising for employing SiNTs as therapeutic platforms.

Plant-Derived Tandem Drug/Mesoporous Silicon Microcarrier Structures for Anti-Inflammatory Therapy.

The properties of nanostructured plant-derived porous silicon (pSi) microparticles as potential candidates to increase the bioavailability of plant extracts possessing anti-inflammatory activity are described in this work. pSi drug carriers were fabricated using an eco-friendly route from the silicon accumulator plant bamboo (tabasheer) powder by magnesiothermic reduction of plant-derived silica and loaded with ethanolic extracts of Equisetum arvense, another silicon accumulator plant rich in polyphenolic compounds. The anti-inflammatory properties of the active therapeutics present in this extract were measured by sensitive luciferase reporter assays; this active extract was subsequently loaded and released from the pSi matrix, with a clear inhibition of the activity of the inflammatory signaling protein NF-κB over a period of hours in a sustained manner. Our results showed that after loading the extracts of E. arvense into pSi microparticles derived from tabasheer, enhanced anti-inflammatory activity was observed owing to enhanced solubility of the extract.

Variation of Optical Properties of Nitrogen-doped Graphene Quantum Dots with Short/Mid/Long-wave Ultraviolet for the Development of the UV Photodetector.

Nitrogen-doped graphene quantum dots (NGQDs) synthesized from a single glucosamine precursor are utilized to develop a novel UV photodetector. Optical properties of NGQDs can be altered with short- (254 nm), mid- (302 nm), and long-wave (365 nm) ultraviolet (UV) exposure leading to the reduction of absorption from deep to mid UV (200-320 nm) and enhancement above 320 nm. Significant quenching of blue and near-IR fluorescence accompanied by the dramatic increase of green/yellow emission of UV-treated NGQDs can be used as a potential UV-sensing mechanism. These emission changes are attributed to the reduction of functional groups detected by Fourier transformed infrared spectroscopy and free-radical-driven polymerization of the NGQDs increasing their average size from 4.70 to 11.20 nm at 60 min treatment. Due to strong UV absorption and sensitivity to UV irradiation, NGQDs developed in this work are utilized to fabricate UV photodetectors. Tested under long-/mid-/short-wave UV, these devices show high photoresponsivity (up to 0.59 A/W) and excellent photodetectivity (up to 1.03 × 1011 Jones) with highly characteristic wavelength-dependent reproducible response. This study suggests that the optical/structural properties of NGQDs can be controllably altered via different wavelength UV treatment leading us to fabricate NGQD-based novel UV photodetectors providing high responsivity and detectivity.

New MRI contrast agents based on silicon nanotubes loaded with superparamagnetic iron oxide nanoparticles.

This article describes the preparation and fundamental properties of a new possible material as a magnetic resonance imaging contrast agent based on the incorporation of preformed iron oxide (Fe3O4) nanocrystals into hollow silicon nanotubes (Si NTs). Specifically, superparamagnetic Fe3O4 nanoparticles of two different average sizes (5 nm and 8 nm) were loaded into Si NTs of two different shell thicknesses (40 nm and 70 nm). To achieve proper aqueous solubility, the NTs were functionalized with an outer polyethylene glycol-diacid (600) moiety via an aminopropyl linkage. Relaxometry parameters r1 and r2 were measured, with the corresponding r2/r1 ratios in phosphate buffered saline confirming the expected negative contrast agent behaviour for these materials. For a given nanocrystal size, the observed r2 values are found to be inversely proportional to NT wall thickness, thereby demonstrating the role of nanostructured silicon template on associated relaxometry properties.