Photodynamic therapy (PDT) is a treatment
modality where light-mediated
activation of photosensitizers in a patient’s body leads to
the generation of cytotoxic reactive oxygen species (ROS), eliminating
cancer cells. One direction that has been firmly established over
past years is the conjugation of photosensitizers with various molecules
that demonstrate their own cytotoxic activity. As a result, improved
selectivity and treatment outcomes are observed compared to those
of unconjugated drugs. The attractiveness of such an approach is due
to the variability of cytotoxic warheads and specific linkers available
for the construction of conjugates. In this review, we summarize and
analyze data concerning these inventions with the ultimate goal to
find a promising conjugation partner for a porphyrinoid-based photosensitizer.
The current challenges toward successful conjugation are also outlined
and discussed. We hope that this review will motivate researchers
to pay closer attention to conjugates and possibilities hidden in
these molecules for the PDT of cancer.
A new water-soluble conjugate, consisting of a chlorin-e 6 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 IC 50 (dark)/IC 50 (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/cm 2 ) produced an excellent therapeutic effect with profound tumor regression and low systemic toxicity.
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