← Back to Search
Functionalized Fullerenes Mediate Photodynamic Killing Of Cancer Cells: Type I Versus Type II Photochemical Mechanism.
P. Mróz, A. Pawlak, Minahil Satti, Haeryeon Lee, T. Wharton, H. Gali, T. Sarna, M. Hamblin
Published 2007 · Medicine, Chemistry
Download PDFAnalyze on Scholarcy
Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetrapyrrole structure of porphyrins, chlorines, and related molecules, but new nontetrapyrrole PS are being sought. Fullerenes are soccer-ball shaped molecules composed of 60 or 70 carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatized with functional groups, whereupon they become soluble and can act as PS. We have compared the photodynamic activity of six functionalized fullerenes with 1, 2, or 3 hydrophilic or 1, 2, or 3 cationic groups. The octanol-water partition coefficients were determined and the relative contributions of Type I photochemistry (photogeneration of superoxide in the presence of NADH) and Type II photochemistry (photogeneration of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin trapping of the superoxide product. We studied three mouse cancer cell lines: (J774, LLC, and CT26) incubated for 24 h with fullerenes and illuminated with white light. The order of effectiveness as PS was inversely proportional to the degree of substitution of the fullerene nucleus for both the neutral and the cationic series. The monopyrrolidinium fullerene was the most active PS against all cell lines and induced apoptosis 4-6 h after illumination. It produced diffuse intracellular fluorescence when dichlorodihydrofluorescein was added as an ROS probe, suggesting a Type I mechanism for phototoxicity. We conclude that certain functionalized fullerenes have potential as novel PDT agents and phototoxicity may be mediated both by superoxide and by singlet oxygen.
This paper references
Current trends in lead discovery: Are we looking for the appropriate properties?
T. Oprea (2002)
Oxygen radicals are generated by dye-mediated intracellular photooxidations: a role for superoxide in photodynamic effects.
J. P. Martin (1987)
Spectroscopy and photophysics of flavin related compounds: Riboflavin and iso-(6,7)-riboflavin
E. Sikorska (2005)
Theoretical property predictions.
D. Livingstone (2003)
Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapy
D. Granville (1998)
Functionalized fullerenes in water. The first 10 years of their chemistry, biology, and nanoscience.
E. Nakamura (2003)
Assessment of the downstream portion of the mitochondrial pathway of caspase activation in patients with acute myeloid leukemia
M. Gronda (2005)
Fullerenes in medicinal chemistry and their biological applications.
N. Tagmatarchis (2001)
Photodynamic therapy in dermatology – an update
P. Babilas (2005)
Cytotoxicity and photocytotoxicity of a dendritic C(60) mono-adduct and a malonic acid C(60) tris-adduct on Jurkat cells.
F. Rancan (2002)
Determinants of the Apoptotic Response to Lysosomal Photodamage
D. Kessel (2000)
Cationic fullerenes are effective and selective antimicrobial photosensitizers.
G. Tegos (2005)
Spin trapping of superoxide.
E. Finkelstein (1979)
SINGLET OXYGEN PRODUCTION FROM FULLERENE DERIVATIVES : EFFECT OF SEQUENTIAL FUNCTIONALIZATION OF THE FULLERENE CORE
T. Hamano (1997)
Photophysical and photobiological processes in the photodynamic therapy of tumours.
M. Ochsner (1997)
H. W. Kroto (1985)
Photodynamic Effect of Polyethylene Glycol–modified Fullerene on Tumor
Y. Tabata (1997)
Matching of chemotherapy to mouse strain and lymphoid tumor type to prevent tumor-induced suppression of specific T- and B-cell functions.
R. Faanes (1979)
A water-soluble β-cyclodextrin derivative possessing a fullerene tether as an efficient photodriven DNA-cleavage reagent
Y. Liu (2005)
Photophysical Characterization and Singlet Oxygen Yield of a Dihydrofullerene
J. Anderson (1994)
A Compilation of Singlet Oxygen Yields from Biologically Relevant Molecules
R. Redmond (1999)
Regulatory pathways in photodynamic therapy induced apoptosis.
P. Agostinis (2004)
Studies on the mechanism of bacteria photosensitization by meso-substituted cationic porphyrins.
M. Merchat (1996)
Establishment of mouse colonic carcinoma cell lines with different metastatic properties.
M. Brattain (1980)
DEFINITION OF TYPE I and TYPE II PHOTOSENSITIZED OXIDATION
C. Foote (1991)
PHOTODYNAMIC THERAPY WITH PHOTOFRIN II INDUCES PROGRAMMED CELL DEATH IN CARCINOMA CELL LINES
X. Y. He (1994)
Direct Near-infrared Luminescence Detection of Singlet Oxygen Generated by Photodynamic Therapy in Cells In Vitro and Tissues In Vivo¶
M. Niedre (2002)
Biological applications of fullerenes.
A. Jensen (1996)
Fullerene derivatives: an attractive tool for biological applications.
S. Bosi (2003)
Electron transfer to triplet fullerene C60
J. Arbogast (1992)
Excited-State Properties of C60 Fullerene Derivatives
D. Guldi (2000)
Distinct steps in DNA fragmentation pathway during camptothecin-induced apoptosis involved caspase-, benzyloxycarbonyl- and N-tosyl-L-phenylalanylchloromethyl ketone-sensitive activities.
A. Sané (1998)
Involvement of nitric oxide during phthalocyanine (Pc4) photodynamic therapy-mediated apoptosis.
S. Gupta (1998)
[Biological activity of photoexcited fullerene].
Y. Yamakoshi (1999)
Photoinactivation of vesicular stomatitis virus with fullerene conjugated with methoxy polyethylene glycol amine.
J. Hirayama (1999)
Photodynamic therapy in oncology.
M. Triesscheijn (2006)
Selective isotopic labeling of a nitroxide spin label to enhance sensitivity for T2 oxymetry
H. Halpern (1990)
Parabolic Quantitative Structure‐Activity Relationships and Photodynamic Therapy: Application of a Three‐Compartment Model with Clearance to the In Vivo Quantitative Structure‐Activity Relationships of a Congeneric Series of Pyropheophorbide Derivatives Used as Photosensitizers for Photodynamic Ther
W. Potter (1999)
Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution.
K. Valko (2004)
Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications.
J. P. Kamat (2000)
Spin trapping of superoxide and hydroxyl radical: practical aspects.
E. Finkelstein (1980)
Targeting antioxidants to mitochondria by conjugation to lipophilic cations.
M. Murphy (2007)
NAD(P)H, a Primary Target of 1O2 in Mitochondria of Intact Cells*
F. Petrat (2003)
Excited-state properties of C(60) fullerene derivatives.
D. Guldi (2000)
Photosensitized oxidation of 2',7'-dichlorofluorescin: singlet oxygen does not contribute to the formation of fluorescent oxidation product 2',7'-dichlorofluorescein.
P. Bilski (2002)
Experimental increase of lung metastases after operative trauma (amputation of limb with tumor).
M. R. Lewis (1958)
Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2-* versus 1O2.
Y. Yamakoshi (2003)
Colorimetric protein assay techniques
C. V. Sapan (1999)
Verteporfin: a milestone in opthalmology and photodynamic therapy
Kirste J Mellish (2001)
Phthalocyanine-sensitized lipid peroxidation in cell membranes: use of cholesterol and azide as probes of primary photochemistry.
G. Bachowski (1991)
Membrane potential and surface potential in mitochondria: Uptake and binding of lipophilic cations
H. Rottenberg (2005)
Blue Light-induced Reactivity of Retinal Age Pigment
M. Rozanowska (1995)
Electron Transfer to Triplet C60
J. Arbogast (1992)
This paper is referenced by
Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity.
M. Ballico (2011)
Application of EPR to porphyrin-protein agents for photodynamic therapy.
Natalya E Sannikova (2020)
Nanocarbon Materials for Photodynamic Therapy and Photothermal Therapy
Q. Li (2014)
Fullerene-porphyrin nanostructures in photodynamic therapy.
C. Constantin (2010)
Modulation of EGFR and ROS induced cytochrome c release by combination of photodynamic therapy and carboplatin in human cultured head and neck cancer cells and tumor xenograft in nude mice.
Heejun Hwang (2013)
Photocytotoxic effect of C60 fullerene against L1210 leukemic cells is accompanied by enhanced nitric oxide production and p38 MAPK activation.
Daria Franskevych (2016)
Fullerene derivatized s-triazine analogues as antimicrobial agents.
Anish Kumar (2009)
Photodynamic therapy (PDT) of cancer: from local to systemic treatment.
J. Dąbrowski (2015)
The use of magnetic field effects on photosensitizer luminescence as a novel probe for optical monitoring of oxygen in photodynamic therapy.
O. Mermut (2009)
Can nanotechnology potentiate photodynamic therapy?
Y. Huang (2012)
Facile fabrication of a C60-polydopamine-graphene nanohybrid for single light induced photothermal and photodynamic therapy.
Z. Hu (2014)
Analytical methods to assess nanoparticle toxicity.
Bryce J. Marquis (2009)
Potassium iodide potentiates antimicrobial photodynamic inactivation mediated by Rose Bengal: in vitro and in vivo studies
X. Wen (2018)
Development of photoactive Sweet-C60 for pancreatic cancer stellate cell therapy.
M. Serda (2018)
Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships.
Kazue Mizuno (2011)
Toxicity of therapeutic nanoparticles.
Melissa A. Maurer-Jones (2009)
Biomedical applications of functionalized fullerene-based nanomaterials
Ranga Partha (2009)
PHOTOACTIVE NANOPARTICLES FOR ONCOLOGY FOTOAKTIVNE NANO^ESTICE U ONKOLOGIJI
Zoran S. Markovi (2010)
Phthalocyanines as medicinal photosensitizers: Developments in the last five years
Xingshu Li (2017)
Characterization of reactive oxygen species generated by protoporphyrin IX under X-ray irradiation
J. Takahashi (2009)
Graphene quantum dots as autophagy-inducing photodynamic agents.
Z. Marković (2012)
Potentiation of photoinactivation of Gram-positive and Gram-negative bacteria mediated by six phenothiazinium dyes by addition of azide ion.
K. R. Kasimova (2014)
Fullerene C60 functionalized γ-Fe2O3 magnetic nanoparticle: Synthesis, characterization, and biomedical applications
Ersin Kılınç (2016)
Features of self-aggregation of C 60 molecules in toluene prepared by different methods
U. K. Makhmanov (2016)
Wave equations without coordinates I: fullerenes
James Avery (2018)
An Experimental and Theoretical Approach to Investigate Correlation between Electromagnetic Properties of Doped Ferrites & its Interfacial Reactivity with Dopamine
Munezza Ata Khan (2020)
Drug Carrier for Photodynamic Cancer Therapy
T. Debele (2015)
Chapter 1 – Antimicrobial photoinactivation with functionalized fullerenes
L. F. Freitas (2016)
Advancing Modern Healthcare With Nanotechnology, Nanobiosensors, and Internet of Nano Things: Taxonomies, Applications, Architecture, and Challenges
Pijush Kanti Dutta Pramanik (2020)
Hybrid photoactive fullerene derivative-ruboxyl nanostructures for photodynamic therapy.
A. I. Kotel’nikov (2013)
Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram‐negative and gram‐positive bacteria
L. Huang (2012)
Reactivities of superoxide and hydroperoxyl radicals with disubstituted cyclic nitrones: a DFT study.
S. Kim (2012)See more