Cobalt bis(dicarbollide) versus closo-dodecaborate in boronated chlorin e(6) conjugates: implications for photodynamic and boron-neutron capture therapyстатья
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Дата последнего поиска статьи во внешних источниках: 16 ноября 2017 г.
Аннотация: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 e6 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 × 108 B/cell) and 27 μM (ca. 2 × 107 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.