Photoactive Fluoropolymer Surfaces That Release Sensitizer Drug Molecules

Abstract

We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer which generates 1O2(1Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/polyvinylalcohol (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, 1O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yields. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only high O2 solubility and drug repellency, but that the C−F bonds physically quench little 1O2 for its productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses of delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT).

Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an ’all‐in‐one' photodynamic device

“…(iii) Figure shows the silica tip with CF 3 CF 2 CF 2 CF 2 groups where facile sensitizer release is expected. For example, PEGylated sensitizer molecules would otherwise adhere to non‐fluorinated silica . Thus, the fluorinated device tip yields repellent characteristics to discharge the sensitizer and also yields high oxygen concentrations consequently producing highly focused quantities of singlet oxygen.…”

“…We and others have observed that polyethylene glycol (PEG) groups bonded to chlorophyll sensitizers can increase their solubility in solution, cell uptake, and phototoxicity in cancer cells. But previous work with chlorin e 6 had required chemically bonding each PEG group individually, with the third PEG adding in low yield (triPEG‐chlorin silica 2 and triPEG‐chlorin Teflon/PVA nanocomposite 3 , Figure ). This led us to pose the question: Can three PEG groups be installed in one step by the use of a galloyl group at its connecting point in tip fabrication ( 1 , Figure )?…”

“…Thus, the aims of the present work were to (i) design a PEG sensitizer based on computed solubility via octanol/water calculations, (ii) fabricate triPEG‐galloyl pheophorbide silica 1 as a new device tip material, and (iii) develop a synthetic approach with fewer steps to reach 1 and with increased stability of the PEG‐sensitizer bond compared to the previously reported 2 and 3 . As we will see, 1 is synthesized in fewer steps, and in higher overall yield and stability compared to 2 and 3 .…”

“… Chemical structures of the new triPEG‐galloyl pheophorbide silica 1 , and previously reported triPEG‐chlorin silica 2 and triPEG‐chlorin Teflon/PVA nanocomposite 3 .…”

S,S‐Chiral Linker Induced U Shape with a Syn‐facial Sensitizer and Photocleavable Ethene Group

“…We hypothesized that the U shape of the bridge would increase the exposure of the ethene site for enhanced 1 O 2 ‐based sensitizer release. We expected this system to be an improvement over our previous succinate and dimethylene‐linked sensitizer photorelease systems. In this system, the 1 O 2 , which triggers the sensitizer release, is generated by the sensitizer surface.…”