Original ArticlePhotoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene Derivatives
Graphical Abstract
Decationically-armed C70 or C84(O2) fullerenes can be excited by UVA, blue, green, white or red light to produce varying amounts of hydroxyl radicals (electron transfer) or singlet oxygen (energy transfer) that can kill cancer cells. Ascorbic acid can potentiate electron transfer but quench singlet oxygen.
Section snippets
Materials
Reagents consisting of γ-butyrolactone, BF3·Et2O, triethylamine, pyridine, iodomethane, 1,8-diazabicyclo[5,4,0]-undec-7-ene (DBU), tetrabromomethane (CBr4), iodine, trifluoroacetic acid, and L-ascorbate were purchased from Aldrich Chemicals and used without further purification. Malonyl chloride was purchased from TCI America. A C70 sample with a purity of 98.0% was purchased from Term USA, Inc. and a C84O2 sample was provided by Nano-C, Inc. Sodium sulfate was employed as a drying agent.
Synthesis of C70- and C84O2-malonate quaternary ammonium iodide salts
The unmodified fullerenes are not soluble in polar solvents, which demands their chemical modification so they can become suited for biological purposes,24 such as PDT. Accordingly, functional moieties of C70 and C84O2 fullerenes were designed to increase both the water-solubility and provide surface binding interactions with –D-Ala-D-Ala residues of the bacteria cell wall by incorporating multiple H-bondings and positive quaternary ammonium charges. We first synthesized a malonate precursor
Discussion
The phenomenon of wavelength-dependent alteration of PDT mechanisms has not been much reported (if at all). When PDT is performed with LC-20 and shorter wavelengths, higher cell killing is achieved, but LC-19-I3− gives higher killing when used along with longer wavelengths, such as red light. The presence of tertiary amine electron donors predisposes towards better killing after short wavelength excitation. Knowing that high amounts of hydroxyl radical induce the apoptosis of cells31 and that
References (51)
- et al.
Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia
J Control Release
(2011) - et al.
Fullerene derivatives: an attractive tool for biological applications
Eur J Med Chem
(2003) - et al.
Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species
J Biol Chem
(2003) - et al.
Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation
FEBS Lett
(2001) - et al.
Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts
Free Radic Biol Med
(1997) - et al.
Lysosomal membrane damage in soluble A beta-mediated cell death in Alzheimer's disease
Neurobiol Dis
(2001) - et al.
Antioxidant and prooxidant properties of ascorbic acid on hepatic dysfunction induced by cold ischemia/reperfusion
Eur J Pharmacol
(2008) - et al.
Ascorbate and plasma membrane electron transport–enzymes vs efflux
Free Radic Biol Med
(2009) - et al.
Biphasic dose-response of antioxidants in hypericin-induced photohemolysis
Photodiagnosis Photodyn Ther
(2011) - et al.
Intracellular flavonoids as electron donors for extracellular ferricyanide reduction in human erythrocytes
Free Radic Biol Med
(2002)
Photodynamic therapy of cancer: an update
CA Cancer J Clin
Photodynamic therapy with fullerenes
Photochem Photobiol Sci
Photodynamic therapy for cancer
Nat Rev Cancer
Photodynamic therapy with fullerenes in vivo: reality or a dream?
Nanomedicine
Photophysical properties of sixty atom carbon molecule (C60)
J Phys Chem
Electron transfer collisions between isolated fullerene dianions and SF6
J Chem Phys
Buckyballs: wide open playing field for chemists
Science
Photodynamic effect of polyethylene glycol-modified fullerene on tumor
Jpn J Cancer Res
Photoinduced charge-separation and charge-recombination processes of fullerene[60] dyads covalently connected with phenothiazine and its trimer
J Phys Chem A
Organic, physical and materials photochemistry
Photoinduced electron transfer between electron donors and fullerenes as unique electron acceptors
Intracellular uptake and photodynamic activity of water-soluble [60]- and [70]fullerenes incorporated in liposomes
Chemistry
Direct and short-time uptake of [70]fullerene into the cell membrane using an exchange reaction from a [70]fullerene-gamma-cyclodextrin complex and the resulting photodynamic activity
Chem Commun (Camb)
Synthesis and photodynamic effect of new highly photostable decacationically armed [60]- and [70]fullerene decaiodide monoadducts to target pathogenic bacteria and cancer cells
J Med Chem
Photoinduced charge and energy transfer involving fullerene derivatives
Photochem Photobiol Sci
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Funding. This work was supported by NIH grant R01CA137108 to LYC. FFS was supported by CAPES Foundation, Ministry of Education of Brazil, grant number 0310-11-5. TD was supported by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421) and a Basic Research Grant from the Orthopaedic Trauma Association (grant 2012-16). MRH was supported by NIH grant RO1AI050875.