Silicon nanoparticles for oral administration of molecular hydrogen.

Medical use of hydrogen gas (H2) has been given increasing attention over the past 15 years with numerous clinical trials for a variety of indications. The biological activity of H2 includes antioxidant properties and thereby the ability to neutralize damaging reactive oxygen species (ROS). Administration of hydrogen as a medical gas is limited by the poor water solubility and by the flammability of H2 in air. Therefore, nanocarriers have been investigated for safer and more efficient administration of hydrogen. Silicon particles are suggested for oral administration with the ability to undergo a redox reaction with water to produce H2in vivo. The purpose of this work was to investigate the hydrogen generating abilities of silicon particles synthesized by centrifugal chemical vapor deposition (cCVD). High hydrogen generation rates up to 1310 ml/g at physiological pH 7.4 (82 % yield) were observed. An in vitro model of oral administration showed that pretreatment in artificial gastric juice did not affect hydrogen generation. Thus, the cCVD silicon particles seem to be suitable for in vivo hydrogen generation. A surface carbon coating or addition of surfactants or albumin hindered hydrogen generation. The addition of egg white reduced hydrogen generation but did not block it.

Post-Acquisition Hyperpolarized 29Silicon Magnetic Resonance Image Processing for Visualization of Colorectal Lesions Using a User-Friendly Graphical Interface.

Medical imaging devices often use automated processing that creates and displays a self-normalized image. When improperly executed, normalization can misrepresent information or result in an inaccurate analysis. In the case of diagnostic imaging, a false positive in the absence of disease, or a negative finding when disease is present, can produce a detrimental experience for the patient and diminish their health prospects and prognosis. In many clinical settings, a medical technical specialist is trained to operate an imaging device without sufficient background information or understanding of the fundamental theory and processes involved in image creation and signal processing. Here, we describe a user-friendly image processing algorithm that mitigates user bias and allows for true signal to be distinguished from background. For proof-of-principle, we used antibody-targeted molecular imaging of colorectal cancer (CRC) in a mouse model, expressing human MUC1 at tumor sites. Lesion detection was performed using targeted magnetic resonance imaging (MRI) of hyperpolarized silicon particles. Resulting images containing high background and artifacts were then subjected to individualized image post-processing and comparative analysis. Post-acquisition image processing allowed for co-registration of the targeted silicon signal with the anatomical proton magnetic resonance (MR) image. This new methodology allows users to calibrate a set of images, acquired with MRI, and reliably locate CRC tumors in the lower gastrointestinal tract of living mice. The method is expected to be generally useful for distinguishing true signal from background for other cancer types, improving the reliability of diagnostic MRI.

Colonic Delivery of α-Linolenic Acid by an Advanced Nutrient Delivery System Prolongs Glucagon-Like Peptide-1 Secretion and Inhibits Food Intake in Mice.

SCOPE: Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L-cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP-1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP-1 release which results in a decrease food intake. METHODS AND RESULTS: α-Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP-1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP-1 secretion. Single-dose orally given αLA loaded mesoporous particles increased plasma active GLP-1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice. CONCLUSIONS: αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.

Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma.

There is a dire need to develop more effective therapeutics to combat brain cancer such as glioblastoma multiforme (GBM). An ideal treatment is expected to target deliver chemotherapeutics to glioma cells across the blood-brain barrier (BBB). The overexpression of transferrin (Tf) receptor (TfR) on the BBB and the GBM cell surfaces but not on the surrounding cells renders TfR a promising target. While porous silicon nanoparticles (pSiNPs) have been intensely studied as a delivery vehicle due to their high biocompatibility, degradability, and drug-loading capacity, the potential to target deliver drugs with transferrin (Tf)-functionalized pSiNPs remains unaddressed. Here, we developed and systematically evaluated Tf-functionalized pSiNPs (Tf@pSiNPs) as a glioma-targeted drug delivery system. These nanoparticles showed excellent colloidal stability and had a low toxicity profile. As compared with nontargeted pSiNPs, Tf@pSiNPs were selective to BBB-forming cells and GBM cells and were efficiently internalized through clathrin receptor-mediated endocytosis. The anticancer drug doxorubicin (Dox) was effectively loaded (8.8 wt %) and released from Tf@pSiNPs in a pH-responsive manner over 24 h. Furthermore, the results demonstrate that Dox delivered by Tf@pSiNPs induced significantly enhanced cytotoxicity to GBM cells across an in vitro BBB monolayer compared with free Dox. Overall, Tf@pSiNPs offer a potential toolbox for enabling targeted therapy to treat GBM.

Scalable submicron/micron silicon particles stabilized in a robust graphite-carbon architecture for enhanced lithium storage.

Silicon-carbon composite is recognized as one of the most promising next-generation anodes for high-energy lithium-ion batteries, especially silicon-graphite composites. Herein, cost-efficient and scalable submicron/micron silicon particles are stabilized in a robust graphite-carbon architecture by solid-phase ball milling and liquid-phase coating methods. The obtained silicon-graphite-carbon composite with a stable encapsulated sandwich-like architecture exhibits impressive lithium storage performance, including high initial Coulombic efficiency of 83.7%, outstanding cycle stability and remarkable rate capability. Even at high loadings of 4 mg cm-2, it still exhibits great reversible capacity with 620 mA h g-1 after 100 cycles at 0.2 C. Furthermore, 8 wt% silicon-graphite-carbon composites as additives are applied into the full cell with a designed capacity of 1000 mA h, and the full cell displays superior cycle stability with high capacity retention of 85% after 100 cycles. In addition, the scalable and low-cost preparation makes it enormous application value and huge commercial prospect.

DNP-NMR of surface hydrogen on silicon microparticles.

Dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) offers a promising route to studying local atomic environments at the surface of both crystalline and amorphous materials. We take advantage of unpaired electrons due to defects close to the surface of the silicon microparticles to hyperpolarize adjacent 1H nuclei. At 3.3 T and 4.2 K, we observe the presence of two proton peaks, each with a linewidth on the order of 5 kHz. Echo experiments indicate a homogeneous linewidth of ∼150-300 Hz for both peaks, indicative of a sparse distribution of protons in both environments. The high frequency peak at 10 ppm lies within the typical chemical shift range for proton NMR, and was found to be relatively stable over repeated measurements. The low frequency peak was found to vary in position between -19 and -37 ppm, well outside the range of typical proton NMR shifts, and indicative of a high-degree of chemical shielding. The low frequency peak was also found to vary significantly in intensity across different experimental runs, suggesting a weakly-bound species. These results suggest that the hydrogen is located in two distinct microscopic environments on the surface of these Si particles.

A Versatile Carbonic Anhydrase IX Targeting Ligand-Functionalized Porous Silicon Nanoplatform for Dual Hypoxia Cancer Therapy and Imaging.

Hypoxia occurs in most solid tumors, and it has been shown to be an independent prognostic indicator of a poor clinical outcome for patients with various cancers. Therefore, constructing a nanosystem specifically targeting cancer cells under hypoxia conditions is a promising approach for cancer therapy. Herein, we develop a porous silicon (PSi)-based nanosystem for targeted cancer therapy. VD11-4-2, a novel inhibitor for carbonic anhydrase IX (CA IX), is anchored on PSi particles (VD-PSi). As CA IX is mainly expressed on the cancer cell membrane under hypoxia condition, this nanocomplex inherits a strong affinity toward hypoxic human breast adenocarcinoma (MCF-7) cells; thus, a better killing efficiency for the hypoxia-induced drug resistance cancer cell is observed. Furthermore, the release of doxorubicin (DOX) from VD-PSi showed pH dependence, which is possibly due to the hydrogen-bonding interaction between DOX and VD11-4-2. The fluorescence resonance energy transfer effect between DOX and VD11-4-2 is observed and applied for monitoring the DOX release intracellularly. Protein inhibition and binding assays showed that VD-PSi binds and inhibits CA IX. Overall, we developed a novel nanosystem inheriting several advantageous properties, which has great potential for targeted treatment of cancer cells under hypoxic conditions.

In Situ Reductive Synthesis of Structural Supported Gold Nanorods in Porous Silicon Particles for Multifunctional Nanovectors.

Porous silicon nanodisks (PSD) were fabricated by the combination of photolithography and electrochemical etching of silicon. By using PSD as a reducing agent, gold nanorods (AuNR) were in situ synthesized in the nanopores of PSD, forming PSD-supported-AuNR (PSD/AuNR) hybrid particles. The formation mechanism of AuNR in porous silicon (pSi) was revealed by exploring the role of pSi reducibility and each chemical in the reaction. With the PSD support, AuNR exhibited a stable morphology without toxic surface ligands (CTAB). The PSD/AuNR hybrid particles showed enhanced plasmonic property compared to free AuNR. Because high-density "hot spots" can be generated by controlling the distribution of AuNR supported in PSD, surface-enhanced raman scattering (SERS) using PSD/AuNR as particle substrates was demonstrated. A multifunctional vector, PSD/AuNR/DOX, composed of doxorubicin (DOX)-loaded PSD/AuNR capped with agarose (agar), was developed for highly efficient, combinatorial cancer treatment. Their therapeutic efficacy was examined using two pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. PSD/AuNR/DOX (20 µg Au and 1.25 µg DOX/mL) effectively destroyed these cells under near-IR laser irradiation (810 nm, 15 J·cm(-2) power, 90 s). Overall, we envision that PSD/AuNR may be a promising injectable, multifunctional nanovector for biomedical application.

Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells.

Nanoporous silicon particles (pSi), with a pore size in the range of 20-60 nm, were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated, with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi particles. These hybrid particles were used as carriers to deliver siRNA to human breast cancer cells. Due to the gradual degradation of the pSi matrix under physiological conditions, the PEI/siRNA nanocomplexes were released from the pore interior in a sustained manner. Physicochemical characterization revealed that the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and narrow particle size distribution between 15 and 30 nm. Gene knockdown against the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene silencing efficacy. Moreover, comprehensive biocompatibility studies were performed for the pSi-PEI/siRNA particles both in vitro and in vivo and demonstrated that the pSi-PEI particles exhibited significantly enhanced biocompatibility. As a consequence, PEI-modified porous silicon particles may have substantial potential as safe and effective siRNA delivery systems.

The experiment study of several resin-removal methods on enamel surface / 重庆医学

Objective To observe the effect of several residual adhesive methods on the enamel surface ,and conduct lab evalua-tion .Methods Sixty premolars extracted because of orthodontic treatment .And all the teeth were randomly divided into 3 groups . Group 1:tungsten carbide burs + silicon particles ;Group 2 :ultrasonic scaling + silicon particles ;Group 3:silicon particles ,each with 20 premolars .After underwent several methods ,the surface roughness differences ,operation time were determined and ob-served with the scanning electron microscope .And the result was statistically analyzed .Results There were significant differences in the surface roughness and operation time among the three groups (P<0 .05) ,The scanning electron microscope after polishing showed that the teeth surface had different degrees of injury ,the silica particles group had less superficial scratch .Conclusion The tungsten carbide burs and ultrasonic instrument for debonding before the silica particles had less superficial scratch .