Light-harvesting ionic dendrimer porphyrins as new photosensitizers for photodynamic therapy.
Photodynamic therapy (PDT) is a promising therapeutic modality for treatment of solid tumors. In this study, third-generation aryl ether dendrimer porphyrins (DPs) with either 32 quaternary ammonium groups (32(+)DPZn) or 32 carboxylic groups (32(-)DPZn) were evaluated as a novel, supramolecular class of photosensitizers for PDT. DPs showed a different cell-association profile depending on the positive or negative charge on the periphery, and both DPs eventually localized in membrane-limited organelles. In contrast, protoporphyrin IX (PIX), which is a hydrophobic and relatively low molecular weight photosensitizer used as a control in this study, diffused through the cytoplasm except the nucleus. Confocal fluorescent imaging using organelle-specific dyes indicated that PIX induced severe photodamage to disrupt membranes and intracellular organelles, including the plasma membrane, mitochondrion, and lysosome. On the other hand, cells treated with DPs kept the characteristic fluorescent pattern of such organelles even after photoirradiation. However, notably 32(+)DPZn achieved remarkably higher (1)O(2)-induced cytotoxicity against LLC cells than PIX. Furthermore, both dendrimer porphyrins had far lower dark toxicity as compared with PIX, demonstrating their highly selective photosensitizing effect in combination with a reduced systemic toxicity.
Nishiyama
Nobuhiro
N
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656, Japan.
Stapert
Hendrik R
HR
Zhang
Guo-Dong
GD
Takasu
Daisuke
D
Jiang
Dong-Lin
DL
Nagano
Tetsuo
T
Aida
Takuzo
T
Kataoka
Kazunori
K
D002462:Cell Membrane / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D007425:Intracellular Membranes / Q000528:radiation effects; D008027:Light; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D015388:Organelles / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000528:radiation effects* / Q000627:therapeutic use; D011166:Porphyrins / Q000493:pharmacokinetics / Q000528:radiation effects* / Q000627:therapeutic use; D026082:Singlet Oxygen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen