Alain Morère

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.

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.

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.

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.

Multifunctionalized mesoporous silica nanoparticles for the in vitro treatment of retinoblastoma: Drug delivery, one and two-photon photodynamic therapy

In this work, we focused on mesoporous silica nanoparticles (MSN) for one photon excitated photodynamic therapy (OPE-PDT) combined with drug delivery and carbohydrate targeting applied on retinoblastoma, a rare disease of childhood. We demonstrate that bitherapy (camptothecin delivery and photodynamic therapy) performed with MSN on retinoblastoma cancer cells was efficient in inducing cancer cell death. Alternatively MSN designed for two-photon excited photodynamic therapy (TPE-PDT) were also studied and irradiation at low fluence efficiently killed retinoblastoma cancer cells.

Quantification of 2-acetyl-1-pyrroline in rice by stable isotope dilution assay through headspace solid-phase microextraction coupled to gas chromatography–tandem mass spectrometry

A new and convenient synthesis of 2-acetyl-1-pyrroline (2AP), a potent flavor compound in rice, and its ring-deuterated analog, 2-acetyl-1-d(2)-pyrroline (2AP-d(2)), was reported. A stable isotope dilution assay (SIDA), involving headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-positive chemical ionization-ion trap-tandem mass spectrometry (GC-PCI-IT-MS-MS), was developed for 2AP quantification. A divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber was used for HS-SPME procedure and parameters affecting analytes recovery, such as extraction time and temperature, pH and salt, were studied. The repeatability of the method (n=10) expressed as relative standard deviation (RSD) was 11.6%. A good linearity was observed from 5.9 to 779 ng of 2AP (r(2)=0.9989). Limits of detection (LOD) and quantification (LOQ) for 2AP were 0.1 and 0.4 ng g(-1) of rice, respectively. The recovery of spiked 2AP from rice matrix was almost complete. The developed method was applied to the quantification of 2AP in aerial parts and grains of scented and non-scented rice cultivars.

Synthesis and Biological Activity of Phosphonate Analogs of Mannose 6-Phosphate (M6P)

Two phosphonate analogs of mannose 6-phosphate (M6P) have been synthesized. The isosteric analog 1 was obtained by a Wittig–Horner reaction at position 6 of a sugar aldehyde. The non-isosteric analog 2 was obtained by a Michaelis–Arbuzov rearrangement of a 6-bromo derivative. In contrast to the non-isosteric analog 2, the isoster 1 was shown to bind to M6P receptors as effectively as does M6P itself, thus demonstrating the considerable potential of the system in drug design.

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.

A new family of potential oncostatics: 2-chloroethylnitrososulfamides (CENS)—I. Synthesis, structure, and pharmacological evaluation (preliminary results)

A new series of alkylating agents, 2-chloroethylnitrososulfamides (CENS), were developed on the model of 2-chloroethylnitrosoureas. Starting from chlorosulfonyl isocyanate, a four-step synthesis (carbamoylation-sulfamoylation, Mitsunobu alkylation, deprotection, and nitrosation) gives the title compounds in a 47-58% overall yield. The selection of the nitrosation site can be directed through an alternative route. The pharmacological evaluation shows a significant oncostatic activity towards both A549 and MCF7 cell lines.