Direct subphthalocyanine conjugation to bombesin vs. indirect conjugation to its lipidic nanocarrier

International audience; Bombesin (BBN) was covalently bound to graftable subphthalocyanine (SubPc) or to a cholesterol derivative, a component of a liposome that encapsulates non-graftable SubPc. The latter bioconjugation approach was suitable to address the stability of SubPc and was achieved by copper-free click-chemistry on the outer-face of the liposome. Liposomes were purified (FPLC) and then analyzed in size (outer diameter about 60 nm measured by DLS). In vitro binding studies allowed to determine the IC50 13.9 nM for one component of the liposome, cholesterol, conjugated to BBN. Hence, azido- (or alkynyl-) liposomes give fluorophores with no reactive functional group available on th…

Phthalocyanine–titanate nanotubes: a promising nanocarrier detectable by optical imaging in the so-called imaging window

International audience; TiONts-phthalocyanine nanohybrids combining an efficient optical probe and a promising nanovector have been developed in a step-by-step approach and were thoroughly characterized. Each 150 nm long TiONts-Pc bear ca. 450 Pc. Three nanohybrids were prepared including three different linkers in quest for the best stability.

Magneto-optical nanomaterials: a SPIO–phthalocyanine scaffold built step-by-step towards bimodal imaging

A SPIO-phthalocyanine nanohybrid is developed as a bimodal contrast agent for Optical and Magnetic Resonance Imaging. The organic coating was covalently attached onto SPIO in a step-by-step approach. Each coated-SPIO was thoroughly characterized. The hydrodynamic size of the SPIO-Pc is ca. 60 nm with a coverage of ca. 690 Pc/SPIO.

NOVEL COMPOUNDS AND USES OF SAME FOR NEAR-INFRARED CHERENKOV LUMINESCENCE IMAGING AND/OR FOR DEEP TISSUE TREATMENT BY CHERENKOV DYNAMIC PHOTOTHERAPY

Harnessing medically relevant metals onto water-soluble subphthalocyanines: towards bimodal imaging and theranostics

International audience; Subphthalocyanine (SubPc), a putative fluorophore for optical imaging (OI), was conjugated to chelating ligands (DOTA, DTPA) affording water-soluble conjugates complexed with (non-radioactive) metals relevant to the following medical imaging techniques/therapies: MRI (Gd), PET (Cu, Ga), SPECT (In, Ga, Lu), RIT (Cu, Lu, Y), and NCT (Gd). Magneto-optical properties of ditopic gadolinium species (and optical properties of other metal containing species) were examined (brightness (ε × Φ F) and relaxivity R 1) and fluorescence confocal/biphoton microscopy studies were conducted. † Electronic supplementary information (ESI) available: Experimental characterization, NMR and…

Synthesis and study of new fluorescent probes for optical imaging, Cherenkov imaging and multimodal imaging

The goal of this work was to prepare and study new fluorescent probes, which could give rise to novel optical or Cherenkov imaging agents. The first section of this work describes the synthesis of fluorescent subphthalocyanines and phthalocyanines probes, which possess relevant chemicals groups suitable for optical imaging applications. The optical and physico-chemical properties of the new probes were carefully examined to ensure they comply with the specification of the fluorophores for the desired application. The second part focused on the subsequent development of a few selected probes into real imaging agents. The biovectorisation of subphtalocyanines was achieved upon conjugation of …

Subphthalocyanines: addressing water-solubility, nano-encapsulation, and activation for optical imaging of B16 melanoma cells

Water-soluble disulfonato-subphthalocyanines (SubPcs) or hydrophobic nano-encapsulated SubPcs are efficient probes for the fluorescence imaging of cells. 20 nm large liposomes (TEM and DLS) incorporated about 13% SubPc. Moreover, some of these fluorophores were found to be pH activatable.

Préparation de liposomes fonctionnels pour l’encapsulation de composés bioactifs ou de sondes moléculaires fluorescentes pour l’imagerie cellulaire

At ICMUB Institute, SUV liposomes have been used to achieve fluorophore encapsulation (subphtalocyanine) for cellular imaging [1] and have been bioconjugated to a peptide (bombesin) to achieve site-specificity, thanks to the structural modification of cholesterol, a component of the liposome, upon introduction of a reactive function. Hence, such liposomes fonctionnalised on the outer face may react with the terminal function of the peptide. Upon purification of the liposome by FPLC a 15 % encapsulation rate was measured by UV/Vis and attempted by ICP. The (outer) diameter of the liposomes (dDLS and dMET) ranged between 20 and 60 nm depending on the type of function or substituents on the ou…

Redshifted Cherenkov Radiation for in vivo Imaging: Coupling Cherenkov Radiation Energy Transfer to multiple Förster Resonance Energy Transfers

AbstractCherenkov Radiation (CR), this blue glow seen in nuclear reactors, is an optical light originating from energetic β-emitter radionuclides. CR emitter 90Y triggers a cascade of energy transfers in the presence of a mixed population of fluorophores (which each other match their respective absorption and emission maxima): Cherenkov Radiation Energy Transfer (CRET) first, followed by multiple Förster Resonance Energy transfers (FRET): CRET ratios were calculated to give a rough estimate of the transfer efficiency. While CR is blue-weighted (300–500 nm), such cascades of Energy Transfers allowed to get a) fluorescence emission up to 710 nm, which is beyond the main CR window and within t…

Subphthalocyanine basicity: reversible protonation at the azomethine bridge

International audience; Subphthalocyanine (SubPc) could be reversibly protonated at the azomethine bridge. This phenomenon was examined by addressing the pKa of the acid (TFA, MSA, TMSA) and the SubPc electron-withdrawing properties of the peripheral isoindolic substituents (F12 vs. H12 and NO2), which tunes the basic character of the azomethine moiety. The protonation of up to three azomethines was suggested and monitored spectrophotometrically with the appearance of new absorption bands at 610, 630 nm and 660 nm, together with marked colour changes from purple to blue to green. Evidence of such a protonation was also shown by significant changes in the 1H-NMR spectrum and new bands in the…

Addressing subphthalocyanines and subnaphthalocyanines features relevant to fluorescence imaging

International audience; A series of new synthetic subphthalocyanines bear structural features aimed at allowing either fluorescence activation or a bathochromic shift of the absorption band towards the near-infrared window, relevant to optical imaging. X-ray diffraction studies of four subphthalocyanines are reported. Spectrofluorimetric studies on subnaphthalocyanines and activatable subphthalocyanine pro-fluorophores are reported.

Inter/intramolecular Cherenkov radiation energy transfer (CRET) from a fluorophore with a built-in radionuclide.

The Cherenkov radiation (CR) from [(18)F]-FDG, [(177)Lu]-LuCl3 and [(90)Y]-YCl3 was detected and CR energy transfer (CRET) to several fluorophores was examined. Subsequent fluorescence emission was found to be a function of the position of absorption bands with respect to the CR peak, energy of emitted particles, radionuclide/fluorophore loading, and fluorophore brightness. A variant of the best fluorophore with a built-in radionuclide was synthesized to achieve inter- and intra-molecular CRET.

Cellular imaging using BODIPY-, pyrene- and phthalocyanine-based conjugates

International audience; Fluorescent Probes aimed at absorbing in the blue/green region of the spectrum and emitting in the green/red have been synthesized (as the form of dyads-pentads), studied by spectrofluorimetry, and used for cellular imaging. The synthesis of phthalocyanine-pyrene 1 was achieved by cyclotetramerization of pyrenyldicyanobenzene, whereas phthalocyanine-BODIPY 2c was synthesized by Sonogashira coupling between tetraiodophthalocyanine and meso-alkynylBODIPY. The standard four-steps BODIPY synthesis was applied to the BODIPY-pyrene dyad 3 starting from pyrenecarbaldehyde and dimethylpyrrole. H-1, C-13, F-19, (BNMR)-B-11, ICP, MS, and UV/Vis spectroscopic analyses demonstra…

CCDC 1014064: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Pascale Winckler, Remi Chassagnon, Philippe Richard, Élodie Gigot, Jean-Marie Perrier-Cornet, Richard A. Decréau|2014|Chem.Commun.|50|13975|doi:10.1039/C4CC05503A

CCDC 1555141: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Philippe Richard, Richard A. Decréau|2018|Tetrahedron|74|1047|doi:10.1016/j.tet.2018.01.029

CCDC 1456530: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Elodie Gigot, Victor Goncalves, Mathieu Moreau, Nicolas Sok, Philippe Richard, Richard A. Decréau|2016|Org.Biomol.Chem.|14|4511|doi:10.1039/C6OB00530F

CCDC 1555144: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Philippe Richard, Richard A. Decréau|2018|Tetrahedron|74|1047|doi:10.1016/j.tet.2018.01.029

CCDC 1555142: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Philippe Richard, Richard A. Decréau|2018|Tetrahedron|74|1047|doi:10.1016/j.tet.2018.01.029

CCDC 1555143: Experimental Crystal Structure Determination

Related Article: Yann Bernhard, Philippe Richard, Richard A. Decréau|2018|Tetrahedron|74|1047|doi:10.1016/j.tet.2018.01.029