Functionalised Fullerenes mediate photo-dynamic killing of cancer cells: Type I versus Type II photochemical mechanism
"In conclusion we have shown that a mono-cationic fullerene is a highly effective PS for killing cancer cells by rapid induction of apoptosis after illumination, and that in contrast to many conventional PS, the photochemical mechanism may involve both Type I and Type II processes"
Photo-dynamic therapy (PDT) employs the combination of non-toxic photo-sensitisers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetra-pyrrole structure of porphyrins, chlorins and related molecules, however, new nontetrapyrrole PS are being sought.
Fullerenes are soccer-ball shaped molecules composed of sixty or seventy carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatised with functional groups, whereupon they become soluble and can act as PS.
We have compared the photo-dynamic activity of six functionalised 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 (photo-generation of super-oxide in the presence of NADH) and Type II photochemistry (photo-generation of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin-trapping of the super-oxide product. We studied three mouse cancer cell lines: (J774, LLC and CT26) incubated for 24 h with fullerenes and illuminated with white light.
To read full abstract, click on the link below:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995806/
QUOTED HIGHLIGHTS:
Various fullerenes, including pristine C60 as well as functionalised derivatives, have been previously used to carry out in vitro PDT reactions leading to: cleavage of DNA strands photo-inactivation of viruses production of oxidative damage to lipids in microsomal membranes PDT-induced killing of mammalian cells in tissue culture and even a report of regressions after PDT in a mouse tumor model
Fullerenes have played a major role as contenders in the search for biological and therapeutic applications of nanotechnology Their extended electron-conjugation system found in C60, makes the molecule absorb visible light, and the first excited singlet state can readily undergo inter-system crossing to the excited triplet state. The photochemical pathway subsequently followed by the fullerene triplet depends heavily on peripheral substituents, the solvent if soluble and the supra-molecular composition of any fullerene particles or aggregates.
In conclusion we have shown that a mono-cationic fullerene is a highly effective PS for killing cancer cells by rapid induction of apoptosis after illumination, and that in contrast to many conventional PS, the photochemical mechanism may involve both Type I and Type II processes.
Acknowledgments:
This work was supported by the US National Institutes of Health (grants R43CA103268 and R44AI68400 to Lynntech Inc, R01CA/AI838801 and R01AI050875 to MRH), and in Poland by Ministry of Science and Higher Education (DS/WBBB/16/06). We are grateful to Professor H.J. Halpern for the gift of mHCTPO.
Photo-dynamic therapy (PDT) employs the combination of non-toxic photo-sensitisers (PS) and harmless visible light to generate reactive oxygen species (ROS) and kill cells. Most clinically studied PS are based on the tetra-pyrrole structure of porphyrins, chlorins and related molecules, however, new nontetrapyrrole PS are being sought.
Fullerenes are soccer-ball shaped molecules composed of sixty or seventy carbon atoms and have attracted interest in connection with the search for biomedical applications of nanotechnology. Fullerenes are biologically inert unless derivatised with functional groups, whereupon they become soluble and can act as PS.
We have compared the photo-dynamic activity of six functionalised 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 (photo-generation of super-oxide in the presence of NADH) and Type II photochemistry (photo-generation of singlet oxygen) were studied by measurement of oxygen consumption, 1270-nm luminescence and EPR spin-trapping of the super-oxide product. We studied three mouse cancer cell lines: (J774, LLC and CT26) incubated for 24 h with fullerenes and illuminated with white light.
To read full abstract, click on the link below:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995806/
QUOTED HIGHLIGHTS:
Various fullerenes, including pristine C60 as well as functionalised derivatives, have been previously used to carry out in vitro PDT reactions leading to: cleavage of DNA strands photo-inactivation of viruses production of oxidative damage to lipids in microsomal membranes PDT-induced killing of mammalian cells in tissue culture and even a report of regressions after PDT in a mouse tumor model
Fullerenes have played a major role as contenders in the search for biological and therapeutic applications of nanotechnology Their extended electron-conjugation system found in C60, makes the molecule absorb visible light, and the first excited singlet state can readily undergo inter-system crossing to the excited triplet state. The photochemical pathway subsequently followed by the fullerene triplet depends heavily on peripheral substituents, the solvent if soluble and the supra-molecular composition of any fullerene particles or aggregates.
In conclusion we have shown that a mono-cationic fullerene is a highly effective PS for killing cancer cells by rapid induction of apoptosis after illumination, and that in contrast to many conventional PS, the photochemical mechanism may involve both Type I and Type II processes.
Acknowledgments:
This work was supported by the US National Institutes of Health (grants R43CA103268 and R44AI68400 to Lynntech Inc, R01CA/AI838801 and R01AI050875 to MRH), and in Poland by Ministry of Science and Higher Education (DS/WBBB/16/06). We are grateful to Professor H.J. Halpern for the gift of mHCTPO.