Marco Ballestri

Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: Effective photoinduced in vitro killing of osteosarcoma

Mesenchymal stem cells (MSC) have the unique ability to home and engraft in tumor stroma. These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma. In the present study, we investigate whether fluorescent core-shell PMMA nanoparticles (FNPs) post-loaded with a photosensitizer, namely meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) and uploaded by MSC could trigger osteosarcoma (OS) cell death in vitro upon specific photoactivation. In co-culture studies we demonstrate using laser confocal microscopy and time lapse imaging, that only after laser irradiation MSC loaded with photosensitizer-coated fluorescent NPs (TPPS@FNPs) undergo cell death and release reactive oxygen species (ROS) which are sufficient to trigger cell death of all OS cells in the culture. These results encourage further studies aimed at proving the efficacy of this novel tri-component system for PDT applications.

5,10-DIHYDRO-SILANTHRENE AS A REAGENT FOR THE BARTON-MCCOMBIE REACTION

Abstract The deoxygenation of secondary alcohols via thionoesters with the use of 5,10-dihydro-silanthrene as the radical reducing agent has been studied in detail. The ability of hydrogen donation of this silane has been measured using the one-carbon ring expansion of 1-(2-oxocyclopentyl)ethyl radical as a timing device.

The reaction of tris(trimethylsilyl)silane with acid chlorides

Abstract Tris(trimethylsilyl)silane, in contrast with tributylin hydridge, reduces acid chlorides to the corresponding decarboxylated hydrocarbons via a free radical mechanism. This methodology could be a viable alternative to Bartons decarboxylation reaction.

(Me3Si)3SiSH: a new radical-based reducing agent

Abstract Tris(trimethylsilyl)silanethiol is an effective and useful reducing agent for some organic substrates. The reduction involves free-radical chain reactions.

TRIS(TRIMETHYLSILYL)SILANE AS MEDIATOR IN THE RADICAL-BASED ALLYLATION REACTIONS OF ALLYL AND 2-FUNCTIONALIZED ALLYL PHENYL SULFONES

Radical allylations with 2-functionalized allyl phenyl sulfones have been performed by using tris(trimethylsilyl)silane as radical mediator. Yields varied from moderate to good depending on the nature of the starting materials. EPR studies on the alkyl radical adducts of allyl sulfones have been performed and conformational information has been obtained for the tert-butyl and tetrahydrofuranyl adducts of 2-carboxy allyl tris(trimethylsilyl)silane.

2-Functionalized allyl tris(trimethylsilyl)silanes as radical-based allylating agents

Abstract Radical allylations with 2-functionalized allyl tris(trimethylsilyl)silanes occur under mild conditions in good to excellent yield provided that the radical precursor and the silane have the appropriate electronic pairing. These reactions offer tin-free altermatives for transformations that are currently conducted with allyl stannanes.

Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model

Purpose Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. Methods Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 μg/mL) and then to SWs (0.43 mJ/mm2 for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. Results There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. Conclusion The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment’s efficacy in an in vitro neuroblastoma model.

Engineered porphyrin loaded core-shell nanoparticles for selective sonodynamic anticancer treatment

AIM Porphyrin-loaded core-shell nanoparticles have been engineered for use as in vivo sonosensitizing systems, radio-tracers or magnetic resonance (MR) imaging agents, which may be suitable for the selective treatment of solid tumors and imaging analyses. MATERIALS & METHODS Polymethyl methacrylate nanoparticles (PMMANPs) have been either loaded with meso-tetrakis (4-sulphonatophenyl) porphyrin (TPPS) for sonodynamic anticancer treatment, with (64)Cu-TPPS for positron emission tomography biodistribution studies or with Mn(III)-TPPS for MR tumor accumulation evaluation. RESULTS PMMANPs are easily functionalized with negatively charged molecules and show favorable biodistribution. In vivo TPPS-PMMANPs have demonstrated shock wave responsiveness in a Mat B III syngeneic rat breast cancer model as measured by MR analyses of pre- and post-treatment tumor volumes. CONCLUSION TPPS-PMMANPs are a multimodal system which can efficiently induce in vivo sonodynamic anticancer activity.

An unexpected stereochemical control of alkene formation by the choice of radical initiator. The reversible addition of (Me3Si)3Si· radicals to alkenes.

Abstract Tris(trimethylsilyl)silyl radical is effective in isomerizing some (Z)-olefins into their thermodynamically more stable (E)-isomers by an addition-elimination path.

Polymer nanoparticles with electrostatically loaded multicargo for combined cancer phototherapy

We have developed a multifunctional polymer-based nanoplatform for bimodal cancer phototherapy. It was achieved by electrostatic entangling of two anionic photoactivable components, a commercial porphyrin and a tailored nitro-aniline derivative, within the cationic shell of polymeric nanoparticles (NPs) based on polymethyl methacrylate. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive agents do not interfere with each other while being in close proximity in the same polymeric scaffold and can thus operate in parallel under the exclusive control of light stimuli. Specifically, visible light triggers satisfactory red fluorescence emission and generation of singlet oxygen (1O2) from one component and release of nitric oxide (NO) from the other. Fluorescence microscopy analysis provides unambiguous evidence for the internalization of the NPs within B78H1 melanoma cells, where they induce amplified mortality due to a combinatory effect of the two photogenerated cytotoxic species.