Jean-Olivier Durand

Mannose-targeted mesoporous silica nanoparticles for photodynamic therapy.

Functionalisation of MSN with mannose for PDT applications dramatically improved the efficiency of PDT on breast cancer cells.

Silica-based nanoparticles for photodynamic therapy applications

Silica-based nanoparticles for applications in photodynamic therapy (PDT) have emerged as a promising field for the treatment of cancer. In this review, based on the pathway the photosensitizer is entrapped inside the silica matrix, the different methods for the synthesis of silica-based nanoparticles are described from the pioneering works to the latest achievements which concern multifunctional nanoplatforms, up-converting nanoparticles, two-photon PDT, vectorization and in vivo applications.

Mannose‐Functionalized Mesoporous Silica Nanoparticles for Efficient Two‐Photon Photodynamic Therapy of Solid Tumors

In the context of national systematic screenings for cancer,photodynamic therapy (PDT) has arisen as an alternative tochemo- and radiotherapy for the non-invasive selectivedestruction of small tumors. PDT involves the use of aphotosensitizer which, upon irradiation at specific wave-lengths, in the presence of oxygen, leads to the generation ofcytotoxic species and consequently to irreversible celldamage.

Biodegradable Ethylene‐Bis(Propyl)Disulfide‐Based Periodic Mesoporous Organosilica Nanorods and Nanospheres for Efficient In‐Vitro Drug Delivery

Periodic mesoporous organosilica nanorods and nanospheres are synthesized from 1,4-bis(triethoxysilyl)ethylene and bis(3-ethoxysilylpropyl)disulfide. The nanosystems present the long-range order of the hexagonal nanostructure. They are degraded in simulated physiological conditions. The loading and release of doxorubicin with these nanosystems are both pH dependent. These nanoparticles are endocytosed by breast cancer cells and are very efficient for doxorubicin delivery in these cells.

Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT.

The synthesis of mesoporous silica nanoparticles (MSN) covalently encapsulating fluoresceine or a photosensitizer, functionalized with galactose on the surface is described. Confocal microscopy experiments demonstrated that the uptake of galactose-functionalized MSN by colorectal cancer cells was mediated by galactose receptors leading to the accumulation of the nanoparticles in the endosomal and lysosomal compartments. The MSN functionalized with a photosensitizer and galactose were loaded with the anti-cancer drug camptothecin. Those MSN combining drug delivery and photodynamic therapy were tested on three cancer cell lines and showed a dramatic enhancement of cancer cell death compared to separate treatments.

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‐Triggered Drug Delivery via Fluorescent Nanovalves

Mesoporous silica nanoparticles (MSN) are functionalized in the walls with an original fluorophore with a high two-photon absorption cross-section. The pores of the MSN filled with anticancer drug are blocked with a pseudo-rotaxane constituted by an azobenzene stalk and a β-cyclodextrin moiety. After incubation of the nanosystem with MCF-7 breast cancer cells, two-photon irradiation at low power is used to image the cells. At high power, cancer cell killing is observed due to the two-photon-triggered opening of the pores through FRET and the release of the anticancer drug from the MSN.

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.

Silicalites and Mesoporous Silica Nanoparticles for photodynamic therapy

The synthesis of silicalites and Mesoporous Silica Nanoparticles (MSN), which covalently incorporate original water-soluble photosensitizers for PDT applications is described. PDT was performed on MDA-MB-231 breast cancer cells. All the nanoparticles showed significant cell death after irradiation, which was not correlated with (1)O(2) quantum yield of the nanoparticles. Other parameters are involved and in particular the surface and shape of the nanoparticles which influence the pathway of endocytosis. Functionalization with mannose was necessary to obtain the best results with PDT due to an active endocytosis of mannose-functionalized nanoparticles. The quantity of mannose on the surface should be carefully adjusted as a too high amount of mannose impairs the phototoxicity of the nanoparticles. Fluorescein was also encapsulated in MCM-41 type MSN in order to localize the nanoparticles in the organelles of the cells by confocal microscopy. The MSN were localized in lysosomes after active endocytosis by mannose receptors.

Two-Photon-Triggered Drug Delivery in Cancer Cells Using Nanoimpellers†

A therapy of cancer cells: Two-photon-triggered camptothecin delivery with nanoimpellers was studied in MCF-7 breast cancer cells. A fluorophore with a high two-photon absorption cross-section was first incorporated in the nanoimpellers. Fluorescence resonance energy transfer (FRET) from the fluorophore to the azobenzene moiety was demonstrated.