pH-dependent chalcogenopyrylium dyes as potential sensitizers for photodynamic therapy: selective retention in tumors by exploiting pH differences between tumor and normal tissue.
Ideal photosensitizers have long-wavelength absorption and strong tumor selectivity with rapid clearance from normal tissues. The telluroselenopyrylium dye 1 that absorbs light at 795 nm (epsilon = 285,000 M-1 cm-1) has a novel property that enhances the tumor specificity and normal tissue clearance. After intralesional injection to both tumors and surrounding skin, it disappeared from the normal skin of BALB/c mice faster than it did from subcutaneously implanted Colon 26 tumors, which resulted in therapeutic selectivity. In vivo reflectance spectroscopy showed that the half-life in tumor was about 50 min while in skin it was around 12 min. This phenomenon appears to be related to the pH differences in normal skin versus tumor, because the rates of drug hydrolysis in solution were shown to be sensitive to changes in pH. Inhibition of tumor regrowth following intratumoral photosensitizer administration depended on both light dose and drug dose, as well as the time interval between dye injection and irradiation; selectivity depended on the time interval. Although treatment parameters were not optimized efficacy was superior to systemic Photofrin under our standard conditions. We discuss how new, more optimal, photosensitizers can be designed that use rates of hydrolysis to exploit the differences in pH between normal tissue and tumor.
Bellnier
D A
DA
PDT Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. bellnier@sc3103.med.buffalo.edu
Young
D N
DN
Detty
M R
MR
Camacho
S H
SH
Oseroff
A R
AR
D000818:Animals; D018011:Chalcogens / Q000493:pharmacokinetics / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018011:Chalcogens; D017319:Photosensitizing Agents