title: Synthesis and evaluation of cationic bacteriochlorin amphiphiles with effectivein vitrophotodynamic activity against cancer cells at low nanomolar concentration.
abstract: Bacteriochlorins are attractive candidates as photosensitizers for photodynamic therapy (PDT) due to their intense absorption in the near-infrared (NIR) region of the spectrum where light transmission through tissue is maximal. Many naturally occurring bacteriochlorins are inherently unstable due to adventitious atmospheric oxidation. Ade novosynthesis affords bacteriochlorins that contain a geminal dimethyl group in each reduced pyrrole ring to increase stability against oxidation. Here, three new synthetic bacteriochlorins, each bearing a single side-chain containing one or two positive charges, were investigated for theirin vitroPDT activity against HeLa human cancer cells. All bacteriochlorins were active at low nanomolar concentration when activated with NIR light; those bearing a single positive charge exhibited faster uptake and higher activity. The bacteriochlorins were localized in mitochondria, lysosomes and endoplasmic reticulum as shown by organelle specific fluorescent probes. Cell death wasviaapoptosis as shown by cell morphology and nuclear condensation. Taken together, the results show the importance of appropriate peripheral groups about a photosensitizer for effective PDT applications.
authors: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Sulbha K
authors: SK
authors: Sharma
authors: Michael
authors: M
authors: Krayer
authors: Felipe F
authors: FF
authors: Sperandio
authors: Liyi
authors: L
authors: Huang
authors: Ying-Ying
authors: YY
authors: Huang
authors: Dewey
authors: D
authors: Holten
authors: Jonathan S
authors: JS
authors: Lindsey
authors: Michael R
authors: MR
authors: Hamblin
keywords: HeLa cancer cells; apoptosis; bacteriochlorins; confocal microscopy; photodynamic therapy; subcellular localization
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