Invited Presentation: 1PA- and 2PA-PDT Photo-Inactivation of Cancer Cells with Deca- or Icosacationic [70]Fullerenes with Light Absorbing e-Donor Antenna

Monday, May 12, 2014: 08:00
Bonnet Creek Ballroom X, Lobby Level (Hilton Orlando Bonnet Creek)
L. Chiang (University of Massachusetts) and M. Hamblin (Harvard Medical School)
We report the synthesis and anticancer photodynamic properties of two new decacationic fullerene (LC14) and red light-harvesting antenna-fullerene conjugated monoadduct (LC15) derivatives. The antenna of LC15 was attached covalently to C60> in a close distance to cage of only <3.0 Ǻ to facilitate ultrafast photoinduced intramolecular electron-transfer (for type-I photochemistry) and photon absorption at long wavelengths up to 600 nm. Because LC15 was more hydrophobic than LC14 we compared formulation in Cremophor EL micelles with direct dilution from dimethylacetamide (DMA). We excited the fullerenes either with UVA (340‒380 nm) or white (400‒700 nm) light and studied their ability to generate singlet oxygen (1O2) and hydroxyl radicals (HO·) using specific fluorescent probes. HeLa human cervical cancer cells were studied in vitro for loss of viability, apoptosis and location of subcellular damage. LC14 produced more 1O2 than LC15, while LC15 produced much more HO· than LC14. When delivered by DMA, LC14 killed more HeLa cells than LC15 when excited by UVA light, while LC15 killed more cells than LC14 when excited by white light consistent with the antenna effect. However LC15 was more effective than LC14 when delivered by micelles regardless of the excitation light. Apoptosis was produced more rapidly after illumination by micellar fullerenes compared to DMA delivery. Intracellular damage was more pronounced after micellar delivery and affected the endoplasmic reticulum as well as lysosomes and mitochondria. These novel structures may be used as photostable photosensitizers for topical application to superficial cancer.