Cobalt bis(dicarbollide) versus closo-dodecaborate in boronated chlorin e6 conjugates: implications for photodynamic and boron-neutron capture therapy

Abstract

Conjugation of boron nanoparticles with porphyrins is an attractive way to create dual agents for anticancer boron neutron capture therapy (BNCT) and photodynamic therapy (PDT). Properties of chlorin e(6) conjugated with two cobalt bis(dicarbollide) nanoparticles (1) or with a closo-dodecaborate nanoparticle (2) are reported. Fluorescent dianionic conjugates 1 and 2 penetrate in A549 human lung adenocarcinoma cells, stain cytoplasm diffusely and accumulate highly in lysosomes but are not toxic themselves for cells. Average cytoplasmic concentration of boron atoms (B) achieves 270 μM (ca. 2 × 10(8) B/cell) and 27 μM (ca. 2 × 10(7) B/cell) at the 1.5 μM extracellular concentration of 1 and 2, respectively, that makes conjugate 1 especially suitable for BNCT. Conjugate 2 causes photoinduced cell death at micromolar concentrations and can be considered also as a photosensitizer for PDT. Conjugates 1 and 2 have high quantum yields of singlet oxygen generation (0.55 and 0.85 in solution, respectively), identical intracellular localization and similar lipid-like microenvironment but conjugate 1 possesses no photoinduced cytotoxicity. A presence of cobalt complexes in conjugate 1 is supposed to be a reason of the observed antioxidative effect in cellular environment, but an exact mechanism of this intriguing phenomenon is unclear. Due to increased intracellular accumulation and absence of photoinduced cytotoxicity conjugate 1 is promising for fluorescence diagnostics of cancer.

Human secreted proteins SLURP‐1 and SLURP‐2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors

“…The Hoechst 33 342/propidium iodide fluorescent microscopy assay was used to evaluate cytotoxic effects of the studied compounds as described earlier (Ignatova et al ., ; Efremenko et al ., ). Cells were stained with 1 μM Hoechst 33 342 (stains nuclei of all cells) and 0.5 μM propidium iodide (stains nuclei of dead cells) in 96‐well microplates and examined using the inverted fluorescence microscope with a long‐working distance 20× objective (Axio Observer, Carl Zeiss AG, Oberkochen, Germany).…”

Organotin Dyes Bearing Anionic Boron Clusters as Cell‐Staining Fluorescent Probes

“…All of the compounds display av ibronic UV/Vis spectrum with am aximum absorption band (l abs )i nt he range 436-440 nm that can be attributed to the HOMO-LUMO electronic transition of the tin complexes with the N-(2-oxido-naphthaldehyde)-4-hydroxybenzohydrazide and as econd absorption band at around 463 nm. [74] The Stokes shifts (Dn)a re around 1000 cm À1 ,i nt he range for molecules that maintain almost the same geometry in the ground and excited states. The only difference is an absorption band at around3 14 nm observed for 7 and 8 attributable to the COSAN moiety.…”

“…Notably,t he higher F F values are for the closo-dodecaborate-bearing compounds 5 and 6,w hereas the lower values are for the COSANd erivatives 7 and 8;s uch ac ontrast in fluorescence quantumy ields has been reported previously. [74] The Stokes shifts (Dn)a re around 1000 cm À1 ,i nt he range for molecules that maintain almost the same geometry in the ground and excited states. [75] In view of the low Stokes shifts, the contribution of internal conversion to the deviationf rom unity of the fluorescenceq uantum yields is expected to be low.I ntersystem crossing is likely to occur, and is probablyf avored by the presence of cobalti n7 and 8.…”

Boronated derivatives of chlorin e 6 and fluoride-containing porphyrins as penetrating anions: a study using bilayer lipid membranes

“…The number of boron atoms in the mol ecule had to be increased so as to increase the thermal neutrons capture cross section and thus increase the effi ciency of compounds in BNCT. It is because of this that porphyrin compounds with different number of carbo [13 15] or dodecaborates [16] in the molecule are being studied now. These compounds are selectively accumulated in cancer cells and can be used both for BNCT and for photodynamic therapy (PDT) of cancer.…”