Emilie Secret

Antibody-Functionalized Porous Silicon Nanoparticles for Vectorization of Hydrophobic Drugs

We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.

Two‐Photon Excitation of Porphyrin‐Functionalized Porous Silicon Nanoparticles for Photodynamic Therapy

Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect.

Anionic porphyrin-grafted porous silicon nanoparticles for photodynamic therapy

Non-toxic porous silicon nanoparticles carry porphyrin covalently attached to their surface inside breast cancer cells for a more efficient photodynamic effect.

Chitosan-functionalized porous silicon optical transducer for the detection of carboxylic acid-containing drugs in water

A chitosan/porous silicon biosensing platform for the detection of carboxylic acid-containing drugs in water is prepared and characterized. Parasitic layer-free films of mesoporous silicon are electrochemically etched and functionalized by covalent attachment of chitosan oligomers. The presence of the chitosan species covering the inner and outer surface of the porous silicon films is confirmed by infrared spectroscopy and nitrogen adsorption analysis. The obtained hybrid platform offers both an important porosity, with a higher surface area than the original porous silicon substrate, and an important surface charge, very suitable for sensing charged molecules. Ibuprofen is chosen as a drug model for the sensing experiments in water. Optical interferometry measurements are performed on the chitosan/porous silicon substrate exposed to ibuprofen solutions of various concentrations, and compared to the same experiments performed on a nonfunctionalized porous silicon surface. Results of the sensing experiments show that the presence of chitosan increases the sensitivity of the sensing porous film by more than one order of magnitude compared to the nonfunctionalized porous film. Detection in water of BHB, a model molecule for illicit rape drug GHB, is also demonstrated at concentrations compatible with forensic analysis, using the chitosan/porous silicon hybrid platform.

Enzyme-Responsive Hydrogel Microparticles for Pulmonary Drug Delivery

Poly(ethylene glycol) based hydrogel microparticles were developed for pulmonary drug delivery. Hydrogels are particularly attractive for pulmonary delivery because they can be size engineered for delivery into the bronchi, yet also swell upon reaching their destination to avoid uptake and clearance by alveolar macrophages. To develop enzyme-responsive hydrogel microparticles for pulmonary delivery a new synthesis method based on a solution polymerization was developed. This method produces spherical poly(ethylene glycol) (PEG) microparticles from high molecular weight poly(ethylene glycol) diacrylate (PEGDA)-based precursors that incorporate peptides in the polymer chain. Specifically, we have synthesized hydrogel microparticles that degrade in response to matrix metalloproteinases that are overexpressed in pulmonary diseases. Small hydrogel microparticles with sizes suitable for lung delivery by inhalation were obtained from solid precursors when PEGDA was dissolved in water at a high concentration. The average diameter of the particles was between 2.8 and 4 μm, depending on the molecular weight of the precursor polymer used and its concentration in water. The relation between the physical properties of the particles and their enzymatic degradation is also reported, where an increased mesh size corresponds to increased degradation.

Initial stem cell adhesion on porous silicon surface: molecular architecture of actin cytoskeleton and filopodial growth

The way cells explore their surrounding extracellular matrix (ECM) during development and migration is mediated by lamellipodia at their leading edge, acting as an actual motor pulling the cell forward. Lamellipodia are the primary area within the cell of actin microfilaments (filopodia) formation. In this work, we report on the use of porous silicon (pSi) scaffolds to mimic the ECM of mesenchymal stem cells from the dental pulp (DPSC) and breast cancer (MCF-7) cells. Our atomic force microscopy (AFM), fluorescence microscopy, and scanning electron microscopy (SEM) results show that pSi promoted the appearance of lateral filopodia protruding from the DPSC cell body and not only in the lamellipodia area. The formation of elongated lateral actin filaments suggests that pores provided the necessary anchorage points for protrusion growth. Although MCF-7 cells displayed a lower presence of organized actin network on both pSi and nonporous silicon, pSi stimulated the formation of extended cell protrusions.

Size Control of Porous Silicon-Based Nanoparticles via Pore-Wall Thinning

Photoluminescent silicon nanocrystals are very attractive for biomedical and electronic applications. Here a new process is presented to synthesize photoluminescent silicon nanocrystals with diameters smaller than 6 nm from a porous silicon template. These nanoparticles are formed using a pore-wall thinning approach, where the as-etched porous silicon layer is partially oxidized to silica, which is dissolved by a hydrofluoric acid solution, decreasing the pore-wall thickness. This decrease in pore-wall thickness leads to a corresponding decrease in the size of the nanocrystals that make up the pore walls, resulting in the formation of smaller nanoparticles during sonication of the porous silicon. Particle diameters were measured using dynamic light scattering, and these values were compared with the nanocrystallite size within the pore wall as determined from X-ray diffraction. Additionally, an increase in the quantum confinement effect is observed for these particles through an increase in the photoluminescence intensity of the nanoparticles compared with the as-etched nanoparticles, without the need for a further activation step by oxidation after synthesis.

Control of the Pore Texture in Nanoporous Silicon via Chemical Dissolution.

The surface and textural properties of porous silicon (pSi) control many of its physical properties essential to its performance in key applications such as optoelectronics, energy storage, luminescence, sensing, and drug delivery. Here, we combine experimental and theoretical tools to demonstrate that the surface roughness at the nanometer scale of pSi can be tuned in a controlled fashion using partial thermal oxidation followed by removal of the resulting silicon oxide layer with hydrofluoric acid (HF) solution. Such a process is shown to smooth the pSi surface by means of nitrogen adsorption, electron microscopy, and small-angle X-ray and neutron scattering. Statistical mechanics Monte Carlo simulations, which are consistent with the experimental data, support the interpretation that the pore surface is initially rough and that the oxidation/oxide removal procedure diminishes the surface roughness while increasing the pore diameter. As a specific example considered in this work, the initial roughness ξ ∼ 3.2 nm of pSi pores having a diameter of 7.6 nm can be decreased to 1.0 nm following the simple procedure above. This study allows envisioning the design of pSi samples with optimal surface properties toward a specific process.