Porous Silicon Nanoparticles Research Articles

Early Cancer Detection and Treatment with Nanotechnology

Until now cancer detection and treatment methods are mostly ineffective due to the following two main reasons. Firstly, patients go to health center when they feel ill, most probably after cancer cells created in their body some long time later and/or the methods by themselves are non-specific screening methods, which often resulted in late cancer detection for effective treatment and some of these methods may be destructive to normal cells or even can cause cancer. Secondly, current cancer treatment methods are non-selection and toxic those kill both abnormal and normal cells leading to serious side effects. The use of nanotechnology to health sector, particularly its ability to detect cancer in its early stage and for complete treatment along with reducing toxicity, promises to have a deep impact on healthcare in general and on cancer in particular. This new technology has already shown the potential to detect cancer in its early stage and to increase the specificity of treatment of tumor cells while leaving healthy cells undamaged through the use of the unique properties of nanoparticles. This review discusses the use of nanoparticles such as quantum dots, magnetic nanoparticles, gold nanoparticles, polymeric micelles, liposomes, dendrimers and porous silicon nanoparticles for the early detection and treatment of cancer.

Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics.

pH stimuli responsive drug delivery platforms that can target specific locations along the gastrointestinal tract hold great promise for colorectal cancer therapy. Herein, we present a facile approach to produce microfluidic engineered pH-sensitive magnetic microspherical carriers containing multifunctional therapeutic payloads for synergistic treatment of colorectal cancer. Chemotherapeutics, 5 fluorouracil (5FU) and curcumin (CUR), were chosen due to their synergistic effect for colorectal cancer treatment and prevention. Drugs were loaded onto naturally derived porous silicon nanoparticles (SiNPs) and magnetic bacterial iron oxide nanowires (BacNWs), which acted as drug nanocontainers and magnetic elements, respectively. Drug loaded SiNPs and BacNWs were then encapsulated into polymeric microspheres using droplet-based microfluidics. To ensure controlled drug delivery into the desired site of action (colon and rectum), the microspheres were fabricated using hypromellose acetate succinate polymers, which are insoluble in the acidic medium of the stomach (i.e. pH 1.2) but soluble at basic pH (colon and rectum). Our results confirmed that the microspheres exhibit a narrow size distribution (CV > 5%) with precise size control. Moreover, in vitro dissolution and drug release data confirmed their pH-responsive properties. Motivated by these results, we explored the biocompatibility of microspheres using human RAW 264.7 macrophages. The results revealed the safety of drug free microspheres up to 1000 μg mL-1. Finally, the synergistic action of 5FU and CUR loaded microspheres was investigated on SW480 colon adenocarcinoma cells.

Preparation and characteristics study of nano-porous silicon UV photodetector

In this study, influence of rapid thermal oxidation RTO and embedding of gold nanoparticles on the performance of porous silicon photodetector synthesised by anodization technique were investigated. Anodization technique was used to fabricate porous silicon photodetector at 10 mA/cm2 for 10 min. The structural, morphological, and photoluminescence properties of porous silicon and gold nanoparticles were investigated. Dark and illuminated current–voltage I–V characteristics, linearity, spectral responsivity, detectivity, and pulsed responsivity of photodetector were investigated before and after RTO and after incorporation of gold nanoparticles. The photosensitivity of nano-porous silicon photodetector at 365 nm was increased from 44 to 154 mA/W and to 200 mA/W at 10 V bias after RTO process and incorporating the gold nanoparticles into the silicon matrix, respectively.

Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB).

Multistaged Nanovaccines Based on Porous Silicon@Acetalated Dextran@Cancer Cell Membrane for Cancer Immunotherapy.

Immunoadjuvant porous silicon (PSi)-based nanovaccines are prepared by nanoprecipitation in a glass capillary microfluidics device. Vesicles, derived from cancer cell membranes encapsulating thermally oxidized PSi nanoparticles or PSi-polymer nanosystems binding a model antigen, are biocompatible over a wide range of concentrations, and show immunostimulant properties in human cells, promoting the expression of co-stimulatory signals and the secretion of pro-inflammatory cytokines.

Quercetin-Based Modified Porous Silicon Nanoparticles for Enhanced Inhibition of Doxorubicin-Resistant Cancer Cells.

One of the most challenging obstacles in nanoparticle's surface modification is to achieve the concept that one ligand can accomplish multiple purposes. Upon such consideration, 3-aminopropoxy-linked quercetin (AmQu), a derivative of a natural flavonoid inspired by the structure of dopamine, is designed and subsequently used to modify the surface of thermally hydrocarbonized porous silicon (PSi) nanoparticles. This nanosystem inherits several advanced properties in a single carrier, including promoted anticancer efficiency, multiple drug resistance (MDR) reversing, stimuli-responsive drug release, drug release monitoring, and enhanced particle-cell interactions. The anticancer drug doxorubicin (DOX) is efficiently loaded into this nanosystem and released in a pH-dependent manner. AmQu also effectively quenches the fluorescence of the loaded DOX, thereby allowing the use of the nanosystem for monitoring the intracellular drug release. Furthermore, a synergistic effect with the presence of AmQu is observed in both normal MCF-7 and DOX-resistant MCF-7 breast cancer cells. Due to the similar structure as dopamine, AmQu may facilitate both the interaction and internalization of PSi into the cells. Overall, this PSi-based platform exhibits remarkable superiority in both multifunctionality and anticancer efficiency, making this nanovector a promising system for anti-MDR cancer treatment.

Delivery of Flightless I Neutralizing Antibody from Porous Silicon Nanoparticles Improves Wound Healing in Diabetic Mice.

Flightless I (Flii) is elevated in human chronic wounds and is a negative regulator of wound repair. Decreasing its activity improves healing responses. Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold significant promise as healing agents. However, to avoid the need for repeated application in a clinical setting and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. In this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for the controlled release of FnAb to diabetic wounds. We achieve FnAb loading regimens exceeding 250 µg antibody per mg of vehicle. FnAb-loaded pSi NPs increase keratinocyte proliferation and enhance migration in scratch wound assays. Release studies confirm the functionality of the FnAb in terms of Flii binding. Using a streptozotocin-induced model of diabetic wound healing, a significant improvement in healing is observed for mice treated with FnAb-loaded pSi NPs compared to controls, including FnAb alone. FnAb-loaded pSi NPs treated with proteases show intact and functional antibody for up to 7 d post-treatment, suggesting protection of the antibodies from proteolytic degradation in wound fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers.

Effect of radiation on the electrical and luminescent properties of conjugated polymer – porous silicon composite

ABSTRACTSystematic evaluation of the influence of simultaneous β- and γ-radiation from radium isotope on the electrical and photoluminescent response of hybrid nanocomposites obtained by adding porous silicon nanoparticles into poly(3,4-ethylenedioxythiophene) doped by poly(styrenesulfonate) host matrix is presented. It was found the decrease in the photoluminescence intensity and increasing the electrical conductivity of hybrid film because of radiation exposure. Radiation-induced changes occur in the polymer as well as in PS nanoparticles contributing simultaneously to the total electrical response. The obtained results expand the perspective of nanocomposite applications for radiation sensing.

Delivery of Flightless I siRNA from Porous Silicon Nanoparticles Improves Wound Healing in Mice.

Flightless I (Flii), a cytoskeletal actin remodelling protein, is elevated in wounds and is a negative regulator of wound healing. Gene silencing using small interfering RNA (siRNA) is an attractive approach to antagonize Flii, and therefore holds significant promise as a therapeutic intervention. The development of siRNA therapeutics has been limited by an inability of the siRNA to cross the cell surface plasma membrane of target cells and also by their degradation due to endogenous nuclease action. To overcome these limitations, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable and high surface area material commonly used for drug delivery applications. Here we investigated the use of pSi nanoparticles (pSiNPs) for the controlled release of Flii siRNA to wounds. Thermally hydrocarbonized pSiNPs (THCpSiNPs) were loaded with Flii siRNA and then coated with a biocompatible chitosan layer. Loading regimens in the order of 50 μg of Flii siRNA per mg of pSi were achieved. The release rate of Flii siRNA was sustained over 35 h. With addition to keratinocytes in vitro, reduced Flii gene expression in conjunction with lowered Flii protein was observed, in concert with increased cell migration and proliferation. A significant improvement in the healing of acute excisional wounds compared to controls was observed from day 5 onward when Flii siRNA-THCpSiNPs were intradermally injected. THCpSiNPs therefore are an effective vehicle for delivering siRNA, and nanoparticle-based siRNA delivery represents a promising therapeutic approach to improve wound healing.

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.

Composite Porous Silicon-Silver Nanoparticles as Theranostic Antibacterial Agents.

A theranostic nanoparticle with biochemically triggered antibacterial activity is demonstrated. Metallic silver is deposited onto porous silicon nanoparticles (pSiNPs) by galvanic displacement. When aqueous diaminesilver ([Ag(NH3)2]+) is used as a silver source, the pSiNPs template the crystalline silver as small (mean diameter 13 nm) and well-dispersed nanoparticles embedded within and on the larger (100 nm) pSiNPs. The silver nanoparticles (AgNPs) quench intrinsic photoluminescence (PL) from the porous silicon (pSi) matrix. When exposed to an aqueous oxidant, the AgNPs are preferentially etched, Ag+ is released into solution, and PL from the pSi carrier is recovered. The released Ag+ results in 90% killing of (Gram-negative) Pseudomonas aeruginosa and (Gram-positive) Staphylococcus aureus within 3 h. When conjugated with the TAT peptide (sequence RKKRRQRRR), the silver-deposited porous silicon (pSi-Ag) nanocomposite shows distinct targeting toward S. aureus bacteria in vitro. Intravenously injected TAT-conjugated pSi-Ag nanoparticles accumulate in the liver, spleen, and lungs of mice, and the in vivo release of Ag+ and recovery of PL from pSi are demonstrated by the subsequent intraperitoneal administration of a hexacyanoferrate solution. The released Ag+ leads to a significant bacterial count reduction in liver tissue relative to the control. The data demonstrate the feasibility of the targeted and triggered delivery of antibacterial Ag+ ion in vivo, using a self-reporting and nontoxic nanocarrier.

Porous silicon nanoparticle as a stabilizing support for chondroitinase

Chondroitinase ABCI (cABCI) from Proteus vulgaris is a drug enzyme that can be used to treat spinal cord injuries. One of the main problems of chondroitinase ABC1 is its low thermal stability. The objective of the current study was to stabilize the enzyme through entrapment within porous silicon (pSi) nanoparticles. pSi was prepared by an electrochemical etch of p-type silicon using hydrofluoric acid/ethanol. The size of nanoparticles were determined 180nm by dynamic light scattering and the mean pore diameter was in the range of 40–60nm obtained by scanning electron microscopy. Enzymes were immobilized on porouse silicon nanoparticles by entrapment. The capacity of matrix was 35μg enzyme per 1mg of silicon. The immobilized enzyme displayed lower Vmax values compared to the free enzyme, but Km values were the same for both enzymes. Immobilization significantly increased the enzyme stability at various temperatures (−20, 4, 25 and 37°C). For example, at 4°C, the free enzyme (in 10mM imidazole) retained 20% of its activity after 100min, while the immobilized one retained 50% of its initial activity. Nanoparticles loading capacity and the enzyme release rate showed that the selected particles could be a pharmaceutically acceptable carrier for chondroitinase.

Sensitive detection of copper ions via ion-responsive fluorescence quenching of engineered porous silicon nanoparticles.

Heavy metal pollution has been a problem since the advent of modern transportation, which despite efforts to curb emissions, continues to play a critical role in environmental pollution. Copper ions (Cu2+), in particular, are one of the more prevalent metals that have widespread detrimental ramifications. From this perspective, a simple and inexpensive method of detecting Cu2+ at the micromolar level would be highly desirable. In this study, we use porous silicon nanoparticles (NPs), obtained via anodic etching of Si wafers, as a basis for undecylenic acid (UDA)- or acrylic acid (AA)-mediated hydrosilylation. The resulting alkyl-terminated porous silicon nanoparticles (APS NPs) have enhanced fluorescence stability and intensity, and importantly, exhibit [Cu2+]-dependent quenching of fluorescence. After determining various aqueous sensing conditions for Cu2+, we demonstrate the use of APS NPs in two separate applications – a standard well-based paper kit and a portable layer-by-layer stick kit. Collectively, we demonstrate the potential of APS NPs in sensors for the effective detection of Cu2+.

Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability.

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

Domino-Like Intercellular Delivery of Undecylenic Acid-Conjugated Porous Silicon Nanoparticles for Deep Tumor Penetration.

Improving the intratumoral distribution of anticancer agents remains the critical challenge for developing efficient cancer chemotherapy. Luminescent porous silicon nanoparticles (PSiNPs) have attracted considerable attention in the biomedical field especially in drug delivery. Here, we described the lysosomal exocytosis-mediated domino-like intercellular delivery of undecylenic acid-conjugated PSiNPs (UA-PSiNPs) for deep tumor penetration. UA-PSiNPs with significantly improved stability in physiological conditions were internalized into tumor cells by macropinocytosis-, caveolae-, and clathrin-mediated endocytosis and mainly colocalized with Golgi apparatus and lysosomes. Substantial evidence showed that UA-PSiNPs was excreted from cells via lysosomal exocytosis after cellular uptake. The exocytosed UA-PSiNPs induced a domino-like infection of adjacent cancer cells and allowed encapsulated doxorubicin (DOX) to deeply penetrate into both three-dimensional tumor spheroids and in vivo tumors. In addition, DOX-loaded UA-PSiNPs exhibited strong antitumor activity and few side effects in vivo. This study demonstrated that UA-PSiNPs as a drug carrier might be applied for deep tumor penetration, offering a new insight into the design of more efficient delivery systems of anticancer drugs.

Synthesis and Characterization of Luminescent Amorphous Porous Silicon (ap-Si) Nanoparticles via unconventional Stain Etching

Starting from crystalline silicon we synthesised bright suspensions of amorphous porous silicon nanoparticles through unconventional stain etching. Upon excitation with UV light, this novel nanostructured material gives rise to an intense red photoluminescence (PL) which resembles that of some silicon nanostructures. We studied the properties of the prepared nanoparticles using a number of cutting-edge characterization techniques such as TEM, SEM and EDX. The complete crystalline-to-amorphous phase transition, confirmed by the morphological studies, seems fortuitous.

GAS SENSORS BASED ON ORGANIC-INORGANIC NANOCOMPOSITES

The use of nanocrystals with large specific surface in sensor structures provides their high sensitivity to molecules of adsorbed gases. The aim of the work was to create sensor elements based on composite films of poly-3,4-ethylenedioxythiophene (PEDOT) in combination with nanocrystals of porous silicon (PS) and zinc oxide (ZnO) and to study the effect of adsorption of ammonia, ethanol and acetone molecules on the electrical parameters of the PEDOT-PS-ZnO structure.To produce film of PEDOT-PS-ZnO hybrid composite, 1% suspension of PEDO-PSS, zinc oxide with a particle size of 100 nm (Sigma-Aldrich Co, USA) and PS nanocrystals, obtained by electrochemical etching of silicon wafer were used. Research of adsorption-desorption processes in the composite films was carried out by measuring their electrical parameters at different concentrations of the analyzed gases. To evaluate the sensor properties, the adsorption sensitivity of the composite films was calculated and their dynamic characteristics were studied.Increase of electrical resistance of nanocomposite due to adsorption of ammonia, ethanol and acetone molecules was registered. The almost linear dependence of the resistance on the concentration of ammonia and acetone was observed. It is a significant advantage in developing of the gas sensors. The maximum sensitivity of the sensor elements is in the range of 1-2% concentration of the analyzed gases and the response time is 60-80 s. The films with higher content of PS nanocrystals were more sensitive to molecules of ammonia and ethanol, and the films containing more nanoparticles of ZnO - to molecules of acetone. To control functional parameters of the sensor films, the content ratio of semiconductor nanoparticles in hybrid composite can be changed.The combination of nanoparticles of porous silicon and zinc oxide provides not only an increase in working surface area of sensors, but also high sensitivity and selectivity to the ammonia, ethanol and acetone molecules. The obtained results can be used to create effective analyzers of gases.

Temperature responsive porous silicon nanoparticles for cancer therapy – spatiotemporal triggering through infrared and radiofrequency electromagnetic heating

One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals. TOC imageThe temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo.

Active diffusion of nanoparticles of maternal origin within the embryonic brain.

To investigate porous silicon (PSi) nanoparticles (NPs) behavior in the embryonic brain. Fluorescently labeled PSi NPs were injected into the embryonic brains intraventricularly and to the mother intravenously (iv.). Brain histology from different time points up to 3 days was analyzed and live brains imaged with two-photon microscopy. PSi NPs were able to penetrate 80% of the embryonic cortical depth. Particle motility was confirmed in real-time in vivo. PSi NPs were able to penetrate the embryonic cortex after either iv. maternal or intraventricular injection. No developmental of macromorphological changes or increased cell apoptosis was observed. PSi NPs penetrate deep in the brain tissues of embryos after intraventricular injection and after iv. injection to the mother.

Porous Silicon Nanoparticles Prepared By an Alkaline Process As an Anode for Use in Lithium Ion Batteries

INTRODUCTION In future, lithium ion batteries (LIBs) for use in electric cars and other applications will be required to provide greater energy densities. At present, silicon (Si) is a candidate anode material for improved, commercially viable batteries, due to its high theoretical capacity (4200 mAh/g) compared to graphite (372 mAh/g). However, the use of Si-based anodes is still restricted because of two problems; the low electrical conductivity of Si, and the significant volume change during lithiation and delithiation. There has been much research devoted to mitigating the deterioration of Si during charging and discharging and to increasing the conductivity of various anode active materials. Recently, several approaches to the synthesis of porous Si-based anode materials that exhibit good cycling properties have been developed. Some of these techniques are based on wet-chemical etching using hydrofluoric acid (HF) and silver nitrate (AgNO3). Ag-deposited Si nanoparticles are initially fabricated using HF and AgNO3. Subsequently, these particles are immersed in a solution containing HF and hydrogen peroxide (H2O2), producing porous Si nanoparticles. However, since HF is quite hazardous, the fabrication of Ag-deposited Si particles without HF would be an improvement.1,2,3) Herein, we describe the preparation of porous Si nanoparticles intended for use as LIB anode materials via both an alkaline method and an alkaline and HF hybrid method. EXPERIMENTAL A planetary ball mill was used to produce Si nanoparticles. These were ultrasonically dispersed for 30 min in an immersion plating bath containing 2 g/L Si, 0.005 M AgNO3 and 0.010 M EDTA-2Na, adjusted to a pH of 9 to 12 with KOH. The reaction was carried out in a water bath at 30 °C for 1 min. In addition, Si nanoparticles were treated using an alkaline and HF hybrid technique.The porous silicon nanoparticles were collected by suction filtration and dried under vacuum at 80 °C for 2 h. The microstructures of the samples were observed using field emission scanning electron microscopy (FE-SEM). Electrochemical characterizations of samples were performed. The working electrodes were composed of the active material, carbon black and polyvinylidene fluoride (PVdF) as a binder, at a 70:15:15 mass ratio. The mixture was subsequently cast onto copper foil and dried under vacuum at 80 °C for 3 h. Coin-type CR 2032 cells were assembled in an argon-filled glove box using a separator and lithium foil as the counter electrode. The electrolyte was 1 M LiPF6 in a mixture of ethylene carbonate (EC) and diethyl carbonate (DEC) (1:1 v/v). The cut off potentials for the charge-discharge processes were 0.02-1.5 V (vs. Li/Li+) and cyclic voltammetry (CV) curves were acquired at room temperature. RESULTS AND DISCUSSION Porous Si nanoparticles were clearly not obtained when using the alkaline method but were fabricated when employing the hybrid approach. Figure 1 shows an SEM image of the nanoparticles resulting from the hybrid method. It is evident that these particles contain numerous nanosized pores. The discharge capacity of these porous Si nanoparticles was much better than that of untreated Si nanoparticles. It is believed that the pores work to mitigate the volume change of the silicon upon insertion. The charge/discharge characteristics of these materials will be detailed in our presentation. Figure 1