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

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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 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.

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Abbreviations

AO:

Acridine orange

BNCT:

Boron neutron capture therapy

BSA:

Bovine serum albumin

CrEL:

Polyoxyethylene derivative of hydrogenated castor oil, Cremophor EL

DNA:

Deoxyribonucleic acid

HSA:

Human serum albumin

PDT:

Photodynamic therapy

PI:

Propidium iodide

RB:

Rose bengal

RNA:

Ribonucleic acid

RNO:

4-Nitroso-N, N-dimethylaniline

ROS:

Reactive oxygen species

Φ:

Quantum yield(s) of singlet oxygen generation

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Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya, 16/10, 117997, Moscow, Russia

    Anastasija V. Efremenko, Anastasija A. Ignatova & Alena A. Borsheva

  2. M.V.Lomonosov Moscow State Academy of Fine Chemical Technology, Vernadskii Prosp. 86, 119571, Moscow, Russia

    Anastasija V. Efremenko, Alena A. Borsheva, Mikhail A. Grin & Andrey F. Mironov

  3. Russian Academy of Sciences, Vavilov Str. 28, 119991, Moscow, Russia

    Vladimir I. Bregadze & Igor B. Sivaev

  4. Biological Faculty, Lomonosov Moscow State University, Vorobyevi Gori 1, Moscow, 119992, Russia

    Alexey V. Feofanov

Authors
  1. Anastasija V. Efremenko
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  2. Anastasija A. Ignatova
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  3. Alena A. Borsheva
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  4. Mikhail A. Grin
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  5. Vladimir I. Bregadze
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  8. Alexey V. Feofanov
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Correspondence to Alexey V. Feofanov.

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Efremenko, A.V., Ignatova, A.A., Borsheva, A.A. et al. Cobalt bis(dicarbollide) versus closo-dodecaborate in boronated chlorin e6 conjugates: implications for photodynamic and boron-neutron capture therapy. Photochem Photobiol Sci 11, 645–652 (2012). https://doi.org/10.1039/c2pp05237g

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