Water-Soluble Chlorin/Arylaminoquinazoline Conjugate for Photodynamic and Targeted Therapy

A new water-soluble conjugate, consisting of a chlorin-e6 photosensitizer part, a 4-arylaminoquinazoline
moiety with affinity to epidermal growth factor receptors, and a hydrophilic
β-d-maltose fragment, was synthesized starting from
methylpheophorbide-a in seven steps. The prepared
conjugate exhibited low levels of dark cytotoxicity and pronounced
photoinduced cytotoxicity at submicromolar concentrations in vitro,
with an IC50(dark)/IC50(light) ratio of ∼368
and a singlet oxygen quantum yield of about 20%. In tumor-bearing
Balb/c nude mice, conjugate 1 preferentially accumulates
in the tumor tissue. Irradiation of the nude mice bearing A431 xenograft
tumors after intravenous administration of the prepared conjugate
with a relatively low light dose (50 J/cm2) produced an
excellent therapeutic effect with profound tumor regression and low
systemic toxicity.