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 (R-7) was conjugated to 5-[4-carboxyphenyl]-10,15,20-triphenyl-2,3-dihydroxychlorin (TPC). The resulting conjugate (R-7-TPC) enhanced intracellulor TPC uptake, which increased proportionally with the incubation time of the conjugate. The water solubility of the highly hydrophobic TPC photo- sensitizer was also improved after conjugation. Increased phototoxicity of R,-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 become prevalent at higher concentrations.