Porous Silicon Nanoparticles Research Articles

Cellular interactions of surface modified nanoporous silicon particles

In this study, the self-assembly of hydrophobin class II (HFBII) on the surface of thermally hydrocarbonized porous silicon (THCPSi) nanoparticles was investigated. The HFBII-coating converted the hydrophobic particles into more hydrophilic ones, improved the particles' cell viability in both HT-29 and Caco-2 cell lines compared to uncoated particles, and enhanced the particles' cellular association. The amount of HFBII adsorbed onto the particles was also successfully quantified by both the BCA assay and a HPLC method. Importantly, the permeation of a poorly water-soluble drug, indomethacin, loaded into THCPSi particles across Caco-2 monolayers was not affected by the protein coating. In addition, (125)I-radiolabelled HFBII did not extensively permeate the Caco-2 monolayer and was found to be stably adsorbed onto the THCPSi nanoparticles incubated in pH 7.4, which renders the particles the possibility for further track-imaging applications. The results highlight the potential of HFBII coating for improving wettability, increasing biocompatibility and possible intestinal association of PSi nanoparticulates for drug delivery applications.

Functionalization of Mesoporous Silicon Nanoparticles for Targeting and Bioimaging Purposes

Carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi‐NP) were synthesized, and their opsonization and targeting properties were studied in vitro alongside with in vivo biodistribution. The carboxyl groups on UnTHCPSi were utilized to further functionalize the nanoparticles. In order to reduce the opsonization of the UnTHCPSi‐NPs, different sized polyethylene glycol (PEG) were conjugated or adsorbed to the NPs surface. The latter approach, based on hydrophobic interaction, turned out to be more effective in reducing the opsonization and improving the stability of the nanoparticle suspension. The most abundant opsonins after plasma incubation were fibrinogen precursors and IgG. Furthermore, the targeting properties of UnTHCPSi‐NPs were studied in vitro with antibodies against glutathione S‐transferase (anti‐GST). PEGylated NPs conjugated with anti‐GST bound to GST‐agarose in human plasma nearly 35‐fold compared to control NPs, indicating that UnTHCPSi‐NPs are suitable for targeting in physiological environment. The in vivo biodistribution in mice revealed that PEGylated UnTHCPSi‐NPs, accumulate fast into the liver and the spleen, regardless of the reduced opsonization in vitro. However, autoradiography and transmission electron microscopy showed that majority of the NPs still remained in hepatic blood vessels and sinusoids suggesting a possibility to utilize them as a sustained release platform for payload molecules.

In-vivo cancer cell destruction using porous silicon nanoparticles

In-vivo animal tests were performed to investigate the feasibility of photothermal therapy based on porous silicon nanoparticles (PSiNPs) in combination with a near-infrared (NIR) laser. The in-vivo animal test results showed that the murine colon carcinoma (CT-26) tumors were completely resorbed with minimal damage to surrounding healthy tissue within 5 days after PSiNPs and NIR laser treatments. In contrast, tumors in the groups treated only with PSiNPs or NIR and a control group continued to grow until the mice died. All of the mice treated with both PSiNPs and NIR remained healthy and free of tumors even 90 days after the treatment. In-vivo fluorescence imaging and the urine and feces tests revealed that PSiNPs injected intratumorally into mice were cleared mainly through the urine. The in-vivo animal test results suggest that thermotherapy based on porous silicon in combination with NIR laser irradiation can efficiently destroy cancer cells selectively without damaging the surrounding healthy cells.

PH-Operated Mechanized Porous Silicon Nanoparticles

Porous silicon nanoparticles (PSiNPs) were synthesized by silver-assisted electroless chemical etching of silicon nanowires generated on a silicon wafer. The rod-shaped particles (200-400 nm long and 100-200 nm in diameter) were derivatized with a cyclodextrin-based nanovalve that was closed at the physiological pH of 7.4 but open at pH <6. Release profiles in water and tissue culture media showed that no cargo leaked when the valves were closed and that release occurred immediately after acidification. In vitro studies using human pancreatic carcinoma PANC-1 cells proved that these PSiNPs were endocytosed and carried cargo molecules into the cells and released them in response to lysosomal acidity. These studies show that PSiNPs can serve as an autonomously functioning delivery platform in biological systems and open new possibilities for drug delivery.

Agarose Surface Coating Influences Intracellular Accumulation and Enhances Payload Stability of a Nano-delivery System

Protein therapeutics often require repeated administrations of drug over a long period of time. Protein instability is a major obstacle to the development of systems for their controlled and sustained release. We describe a surface modification of nanoporous silicon particles (NSP) with an agarose hydrogel matrix that enhances their ability to load and release proteins, influencing intracellular delivery and preserving molecular stability. We developed and characterized an agarose surface modification of NSP. Stability of the released protein after enzymatic treatment of loaded particles was evaluated with SDS-page and HPLC analysis. FITC-conjugated BSA was chosen as probe protein and intracellular delivery evaluated by fluorescence microscopy. We showed that agarose coating does not affect NSP protein release rate, while fewer digestion products were found in the released solution after all the enzymatic treatments. Confocal images show that the hydrogel coating improves intracellular delivery, specifically within the nucleus, without affecting the internalization process. This modification of porous silicon adds to its tunability, biocompatibility, and biodegradability the ability to preserve protein integrity during delivery without affecting release rates and internalization dynamics. Moreover, it may allow the silicon particles to function as protein carriers that enable control of cell function.

Abstract 5294: Real-time optical imaging of nanoparticle biodistribution in vivo

Abstract High-resolution optical imaging provides the opportunity to visualize the transport of systemically injected nanoparticle systems along a series of biophysical barriers to their site of action. Data collected using this approach can be used to simulate, predict, understand, and improve the delivery of therapeutics and/or contrast agents to solid tumors. Here we present evidence that tailoring the physical properties of nanoparticle systems can improve their accumulation at disease sites. Using confocal technologies, we investigated the dynamics of nanoporous silicon particles in the microvasculature of normal and tumor-bearing mice. The biodistribution of intravenously injected particles of different size, shape, and surface properties were monitored in real-time. In organs of the reticuloendothelial system (RES), the rate of particle accumulation, as well as the total number of particles accumulated, was highly dependent on particle shape. Particles which preferentially accumulated in tumors were different than those which accumulated in the RES organs, suggesting that particle shape is an important design parameter for organ-specific delivery. The importance of modifying particle surface was evaluated in melanoma-bearing mice by systemically administering particles with and without endothelial-specific targeting moieties. The addition of targeting moieties was found to improve tumor-specific accumulation as much as changing particle shape. We have independently validated these in vivo findings and begun to elucidate the mechanisms of particle accumulation using inductively coupled plasma atomic emission spectrometry, immunocytochemistry, immunohistochemistry, and mathematical modeling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5294. doi:10.1158/1538-7445.AM2011-5294

Porous silicon nanoparticles for cancer photothermotherapy

The in vitro cell tests and in vivo animal tests were performed to investigate the feasibility of the photothermal therapy based on porous silicon (PSi) in combination with near-infrared (NIR) laser. According to the Annexin V- fluorescein isothiocyanate Apoptosis assay test results, the untreated cells and the cells exposed to NIR laser without PSi treatment had a cell viability of 95.6 and 91.3%, respectively. Likewise, the cells treated with PSi but not with NIR irradiation also had a cell viability of 74.4%. Combination of these two techniques, however, showed a cell viability of 6.7%. Also, the cell deaths were mostly due to necrosis but partly due to late apoptosis. The in vivo animal test results showed that the Murine colon carcinoma (CT-26) tumors were completely resorbed without nearly giving damage to surrounding healthy tissue within 5 days of PSi and NIR laser treatment. Tumors have not recurred at all in the PSi/NIR treatment groups thereafter. Both the in vitro cell test and in vivo animal test results suggest that thermotherapy based on PSi in combination with NIR laser irradiation is an efficient technique to selectively destroy cancer cells without damaging the surrounding healthy cells.

Porous Silicon Nanoparticle Photosensitizers for Singlet Oxygen and Their Phototoxicity against Cancer Cells

Porous Si nanoparticles, prepared from electrochemically etched single crystal Si wafers, function as photosensitizers to generate (1)O(2) in ethanol and in aqueous media. The preparation conditions for the porous Si nanoparticles were optimized to maximize (1) the yield of material; (2) its quantum yield of (1)O(2) production; and (3) its in vitro degradation properties. The optimal formulation was determined to consist of nanoparticles 146 ± 7 nm in diameter, with nominal pore sizes of 12 ± 4 nm. The quantum yield for (1)O(2) production is 0.10 ± 0.02 in ethanol and 0.17 ± 0.01 in H(2)O. HeLa or NIH-3T3 cells treated with 100 μg/mL porous Si nanoparticles and exposed to 60 J/cm(2) white light (infrared filtered, 100 mW/cm(2) for 10 min) exhibit ∼45% cell death, while controls containing no nanoparticles show 10% or 25% cell death, respectively. The dark control experiment yields <10% cytotoxicity for either cell type.

Photoconductivity of Polymeric Composites Doped with Porous Silicon Nanoparticles and Additions of Ionic Polymethine Dyes of Different Types

Features of the electrical conductivity and the photoconductivity of polyvinylbutyral films containing silicon nanoparticles and similar films doped with cationic and anionic polymethine dyes are studied. Sensitization of the photoelectric effect by dyes with various ionicities in films is explained by the possible photogeneration of holes and electrons from dye molecules and the intrinsic bipolar conductivity of silicon nanoparticles. It is assumed that the electronic conductivity in silicon nanoparticles is higher as compared with that in nanoparticles with p-type conductivity.

Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. ...

Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. Further quantification of S1MPs in the major organs of the animals by elemental analysis of silicon using inductively coupled plasma-atomic electron spectroscopy verified the accuracy of in vivo near-infrared imaging as a tool for evaluation of nanovector biodistribution.

Hydroxyapatite formation on metallurgical grade nanoporous silicon particles

Studies into bone-like apatite or hydroxyapatite (HA) growth on potential biomaterials when in contact with simulated body fluid (SBF) not only establish a general method for determining bioactivity but coincidently lead to the design of new bioactive materials in biomedical and tissue engineering fields. Previous studies of HA growth on porous silicon (PS) have examined electrochemically etched silicon substrates after immersion in a SBF. This study differs from previous work in that it focuses on characterising HA growth on chemically etched metallurgical grade nanoporous silicon particles. The PS used in this study is comprised of nanosponge particles with disordered pore structures with pore sizes ranging up to 10 nm on micron-sized particles. The silicon particles are analysed before and after immersion into SBF using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) analysis and X-ray photoelectron spectroscopy (XPS). Results indicate that a HA layer forms on the surface of the nanosponge particles. Experimental analysis indicates that the morphology and calcium-to-phosphorus ratio (Ca/P) verify the formation of crystalline HA on the nanoporous silicon particles.

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Porous silicon (PSi) particles have been studied for the effects they elicit in Caco-2 and RAW 264.7 macrophage cells in terms of toxicity, oxidative stress, and inflammatory response. The most suitable particles were then functionalized with a novel (18)F label to assess their biodistribution after enteral and parenteral administration in a rat model. The results show that thermally hydrocarbonized porous silicon (THCPSi) nanoparticles did not induce any significant toxicity, oxidative stress, or inflammatory response in Caco-2 and RAW 264.7 macrophage cells. Fluorescently labeled nanoparticles were associated with the cells surface but were not extensively internalized. Biodistribution studies in rats using novel (18)F-labeled THCPSi nanoparticles demonstrated that the particles passed intact through the gastrointestinal tract after oral administration and were also not absorbed from a subcutaneous deposit. After intravenous administration, the particles were found mainly in the liver and spleen, indicating rapid removal from the circulation. Overall, these silicon-based nanosystems exhibit excellent in vivo stability, low cytotoxicity, and nonimmunogenic profiles, ideal for oral drug delivery purposes.

Reflective and Magnetic Properties of Photonic Polymer Composite Materials Based on Porous Silicon and Magnetite Nanoparticles

Photonic polymer composite materials exhibiting both reflective and magnetic properties were prepared by the replication of rugate porous silicon (PS) using polystyrene and magnetite nanoparticle (Fe3O4). Rugate PS prepared by applying a computer-generated pseudo-sinusoidal current waveform resulted in a mirror with high reflectivity in a specific narrow spectral region and served as a template for replicating its nanostructure with polystyrene containing the magnetic nanoparticles of magnetite. The composite films replicated a sharp photonic resonance with full-width at half maximum (FWHM) of 20 nm from rugate PS in the reflectivity spectrum as well as displayed a magnetic property of magnetite nanoparticles in SQUID magnetometry. Optical characteristics of composite films indicated that the surface of polymer film had a negative structure of rugate PS. The composite films were stable in aqueous solutions for several days without any degradation.

Quantitative Analysis of an Antioxidant Additive in Insoluble Plastics by Surface-Assisted Laser Desorption/Ionization Mass Spectrometry (SALDI-MS) Using TiO2 Nanoparticles

The applicability of matrix-free surface-assisted laser desorption/ionization mass spectrometry using porous silicon (DIOS-MS) and TiO2 nanoparticles (TiO2-SALDI-MS) was examined by analyzing an antioxidant added to insoluble polypropylene (PP) materials. The optimized solvent extraction, which involved freezing and crushing the PP, results in a good recovery, 89±4 and 97±8% for 0.5 wt% of the added antioxidant, tetrakis[methylene3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate]methane (commercial name; Irganox1010) in laboratory-produced and commercial PP composites, respectively. The positive ion measurements in DIOS and TiO2-SALDI-MS yielded sodium adduct ions without any interference from other signals. Using an internal standard with a similar structure, a good calibration curve linearity was established in the Irganox1010 concentration range of 0.01-2.0 mg/mL in PP, which was sufficient for monitoring the plastic additives. However, TiO2-SALDI-MS was superior to DIOS-MS in terms of mass resolution and easiness of sample preparation. A solvent extraction method followed by TiO2-SALDI-MS appears to be a anticipated method for the analysis of additives in insoluble plastics.

Photoconductivity of organic polymer films doped with porous silicon nanoparticles and ionic polymethine dyes

Features of electrical conductivity and photoconductivity of polyvinylbutyral films containing porous silicon nanoparticles and similar films doped with cationic and anionic polymethine dyes are studied. Sensitization of the photoelectric effect by dyes with different ionicities in films is explained by the possible photogeneration of holes and electrons from dye molecules and the intrinsic bipolar conductivity of porous silicon nanoparticles. It is assumed that the electronic conductivity in porous silicon nanoparticles is higher in comparison with p-type conductivity.

Biodegradable luminescent porous silicon nanoparticles for in vivo applications

Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared by the mononuclear phagocytic system before finding their targets, increasing the likelihood of unintended acute or chronic toxicity. However, there has been little effort to engineer the self-destruction of errant nanoparticles into non-toxic, systemically eliminated products. Here, we present luminescent porous silicon nanoparticles (LPSiNPs) that can carry a drug payload and of which the intrinsic near-infrared photoluminescence enables monitoring of both accumulation and degradation in vivo. Furthermore, in contrast to most optically active nanomaterials (carbon nanotubes, gold nanoparticles and quantum dots), LPSiNPs self-destruct in a mouse model into renally cleared components in a relatively short period of time with no evidence of toxicity. As a preliminary in vivo application, we demonstrate tumour imaging using dextran-coated LPSiNPs (D-LPSiNPs). These results demonstrate a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications.

Investigation of polarization anisotropy in individual porous silicon nanoparticles

Polarization anisotropy is investigated in single porous silicon nanoparticles containing multiple chromophores. Two forms of nanoparticle samples are studied; low current density (LCD) and high current density (HCD). Photoluminescence measurements reveal that LCD samples exhibit red-shifted spectra and HCD particles display a blue-shifted spectrum. We utilize single molecule spectroscopy to detect the polarization effects of spatially isolated individual nanoparticles, and show that LCD nanoparticles demonstrate strong polarization anisotropy, whereas a dynamic polarization response is collected from HCD nanoparticles.

Optical Anisotropy in Individual Porous Silicon Nanoparticles Containing Multiple Chromophores

Polarization anisotropy is investigated in single porous silicon nanoparticles containing multiple chromophores. Two classes of nanoparticles, low current density and high current density, are studied. Low current density samples exhibit red-shifted spectra and contain only one or two chromophores. High current density particles, on average, contain less than four chromophores and display a blue-shifted spectrum. We utilize single-molecule spectroscopy to probe the polarization effects of the particles, and we show that both classes of particles are influenced by a polarized excitation source. These results are exciting at the fundamental level for understanding coupled quantum dot emitters as well as for applications involving single-photon sources or silicon-based polarization-sensitive detectors.

Use of NMR Spectroscopy in the Synthesis and Characterization of Air- and Water-Stable Silicon Nanoparticles from Porous Silicon

Air- and water-stable silicon nanocrystals were prepared by the bromine oxidation of porous silicon nanoparticles followed by reaction with n-butyllithium. Transmission electron microscopy suggests that the vigorous oxidation of porous silicon under reflux conditions removes the porous layer from the nanoparticle to expose a crystalline silicon core that can be passivated with organic ligands. A combination of infrared, ultraviolet/visible, and photoluminescence demonstrate the presence of small crystalline silicon particles and saturated hydrocarbon ligands, while solid- and liquid-state nuclear magnetic resonance spectroscopies establish that butyl ligands are localized on the nanocrystal surface. All of these analytical methods suggest that the product of this synthesis is stable in air and water indefinitely.