pH-dependent chalcogenopyrylium dyes as potential sensitizers for photodynamic therapy: Selective retention in tumors by exploiting pH differences between tumor and normal tissue
Da. Bellnier et al., pH-dependent chalcogenopyrylium dyes as potential sensitizers for photodynamic therapy: Selective retention in tumors by exploiting pH differences between tumor and normal tissue, PHOTOCHEM P, 70(4), 1999, pp. 630-636
Ideal photosensitizers have long-wavelength absorption and strong tumor sel
ectivity with rapid clearance from normal tissues. The telluroselenopyryliu
m dye 1 that absorbs light at 795 nm (epsilon = 285 000 M-1 cm(-1)) has a n
ovel property that enhances the tumor specificity and normal tissue clearan
ce. After intralesional injection to both tumors and surrounding skin, it d
isappeared from the normal skin of BALB/c mice faster than it did from subc
utaneously implanted Colon 26 tumors, which resulted in therapeutic selecti
vity. In who reflectance spectroscopy showed that the half-life in tumor wa
s 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 th
e rates of drug hydrolysis in solution were shown to be sensitive to change
s in pH. Inhibition of tumor regrowth;th following intratumoral photosensit
izer administration depended on both light dose and drug dose, as well as t
he time interval between dye injection and irradiation; selectivity depende
d on the time interval. Although treatment parameters were not optimized ef
ficacy was superior to systemic Photofrin(R) under our standard conditions.
We discuss how new, more optimal, photosensitizers can be designed that us
e rates of hydrolysis to exploit the differences in pH between normal tissu
e and tumor.