Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy.
To improve the efficiency of intracellular delivery of photosensitizers and the efficacy of photodynamic therapy, a membrane-penetrating arginine oligopeptide (R7) was conjugated to 5-[4-carboxyphenyl]-10,15,20-triphenyl-2,3-dihydroxychlorin (TPC). The resulting conjugate (R7-TPC) enhanced intracellular TPC uptake, which increased proportionally with the incubation time of the conjugate. The water solubility of the highly hydrophobic TPC photosensitizer was also improved after conjugation. Increased phototoxicity of R7-TPC was observed after an incubation time of only 30 min. Tumor cells mainly underwent apoptosis at lower concentrations of the photosensitizer-polyarginine conjugate, whereas necrotic cell damage became prevalent at higher concentrations.
Choi
Yongdoo
Y
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 149 13th St., Rm. 5406, Charlestown, MA 02129, USA.
McCarthy
Jason R
JR
Weissleder
Ralph
R
Tung
Ching-Hsuan
CH
D001120:Arginine / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry* / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use*; D013056:Spectrophotometry, Ultraviolet
D009842:Oligopeptides; D017319:Photosensitizing Agents; D001120:Arginine