Frédérique Cunin

Oxidation-triggered release of fluorescent molecules or drugs from mesoporous Si microparticles

The fluorescent dye Alexa Fluor 488 or the anticancer drug doxorubicin is attached to the surface and inner pore walls of mesoporous Si particles by covalent attachment, and the oxidation-induced release of each molecule is studied. The molecules are bound to the Si matrix using a 10-undecenoic acid linker, which is attached by thermal hydrosilylation. Loading capacity of the microparticles using this method is approximately 0.5 and 45 mg/g of porous Si microparticle for Alexa Fluor 488 and doxorubicin, respectively. The Si-C-bound assembly is initially stable in aqueous solution, although oxidation of the underlying Si matrix results in conversion to silicon oxide and slow release of the linker-molecule complex by hydrolysis of the Si-O attachment points. When the attached molecule is a fluorophore (Alexa Fluor 488 or doxorubicin), its fluorescence is effectively quenched by the semiconducting silicon matrix. As the particle oxidizes in water, the fluorescence intensity of the attached dye increases due to growth of the insulating silicon oxide layer and, ultimately, dye release from the surface. The recovery of fluorescence in the microparticle and the release of the molecule into solution are monitored in real-time by fluorescence microscopy. Both processes are accelerated by introduction of the oxidizing species peroxynitrite to the aqueous solution. The oxidation-triggered release of the anticancer drug doxorubicin to HeLa cells is demonstrated.

Intravitreal properties of porous silicon photonic crystals: a potential self-reporting intraocular drug-delivery vehicle.

Aim: To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. Methods: A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. Results: No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion: The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.

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.

Study of the optical properties of a thermoresponsive polymer grafted onto porous silicon scaffolds

In this report, a polymer-filled porous silicon (pSi) structure is described that is able to detect changes in temperature around a critical value en route to developing a temperature sensor deployed in wounds dressings that signals inflammation or infection of the wound bed. Using surface-initiated atom transfer radical polymerization (SI-ATRP), thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains are grafted onto pSi layers with different porosity and pore size and the optical changes (effective optical thickness below and above the lower critical solution temperature (LCST)) are monitored via interferometric reflectance spectroscopy. Six etching conditions and three different surface functionalization conditions are explored in order to optimise the optical response to temperature change. Thermally oxidised pSi samples with the highest investigated porosity (80%) show the largest optical response and will be the target for developing optical sensors of wound temperature.

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.

Ruthenium(II) complex-photosensitized multifunctionalized porous silicon nanoparticles for two-photon near-infrared light responsive imaging and photodynamic cancer therapy

Multifunctionalized porous silicon nanoparticles (pSiNPs), containing the novel Ru(ii) complex-photosensitizer, the polyethylene glycol moiety, and mannose molecules as cancer targeting ligands, are constructed and showcased for application in near infrared (NIR) light-responsive photodynamic therapy (PDT) and imaging of cancer. Exposure to NIR light leads to two-photon excitation of the Ru(ii)-complex which allows efficient simultaneous cancer-imaging and targeted PDT therapy with the functionalized biodegradable pSiNP nanocarriers.

Covalent crosslinking of 1-D photonic crystals of microporous Si by hydrosilylation and ring-opening metathesis polymerization

Free-standing porous Si multilayer dielectric mirrors, prepared by electrochemical etching of crystalline Si, are treated with a ruthenium ring-opening metathesis polymerization (ROMP) catalyst followed by norbornene to produce flexible, stable composite materials in which poly(norbornene) is covalently attached to the porous Si matrix.

Characterization of phospholipid bilayer formation on a thin film of porous SiO2 by reflective interferometric Fourier transform spectroscopy (RIFTS).

Classical methods for characterizing supported artificial phospholipid bilayers include imaging techniques such as atomic force microscopy and fluorescence microscopy. The use in the past decade of surface-sensitive methods such as surface plasmon resonance and ellipsometry, and acoustic sensors such as the quartz crystal microbalance, coupled to the imaging methods, have expanded our understanding of the formation mechanisms of phospholipid bilayers. In the present work, reflective interferometric Fourier transform spectrocopy (RIFTS) is employed to monitor the formation of a planar phospholipid bilayer on an oxidized mesoporous Si (pSiO(2)) thin film. The pSiO(2) substrates are prepared as thin films (3 μm thick) with pore dimensions of a few nanometers in diameter by the electrochemical etching of crystalline silicon, and they are passivated with a thin thermal oxide layer. A thin film of mica is used as a control. Interferometric optical measurements are used to quantify the behavior of the phospholipids at the internal (pores) and external surfaces of the substrates. The optical measurements indicate that vesicles initially adsorb to the pSiO(2) surface as a monolayer, followed by vesicle fusion and conversion to a surface-adsorbed lipid bilayer. The timescale of the process is consistent with prior measurements of vesicle fusion onto mica surfaces. Reflectance spectra calculated using a simple double-layer Fabry-Perot interference model verify the experimental results. The method provides a simple, real-time, nondestructive approach to characterizing the growth and evolution of lipid vesicle layers on the surface of an optical thin film.