Abstract:
Di-cationic Zn(II)-phthalocyanines (ZnPcs) are promising photosensitizers for the photodynamic
therapy
(PDT)
of
cancers
and
for
photoinactivation
of
viruses
and
bacteria.
Pegylation
of
photosensitizers
in
general
enhances
their
water-solubility
and
tumor
cell
accumulation.
A
series
of
pegylated
di-cationic
ZnPcs
were
synthesized
from
conjugation
of
a
low
molecular
weight
PEG group to a pre-formed Pc macrocycle, or by mixed condensation involving a
pegylated phthalonitrile. All pegylated ZnPcs were highly soluble in polar organic solvents but
were insoluble in water; they have intense Q absorptions centered at 680 nm and fluorescence
quantum
yields
of
ca.
0.2
in
DMF.
The
non-pegylated
di-cationic
ZnPc
6a
formed
large
aggregates,
which were visualized by atomic force microscopy. The cytotoxicity, cellular
uptake and subcellular distribution of all cationic ZnPcs were investigated in human carcinoma
HEp2 cells. The most phototoxic compounds were found to be the -substituted Pcs. Among
these, Pcs 4a and 16a were the most effective (IC50 ca. 10 M at 1.5 J/cm
), in part due to the
presence of a PEG group and the two positive charges in close proximity (separated by an
ethylene group) in these macrocycles. The β-substituted ZcPcs 6b and 4b accumulated the
most within HEp2 cells but had low photocytoxicity (IC50 > 100 M at 1.5 J/cm
2
), possibly as
a result of their lower electron density of the ring and more extended conformations compared
with
the
-substituted
Pcs.
The
results
show
that
the
charge
distribution
about
the
Pc
macrocycle
and the intracellular localization of the cationic ZnPcs mainly determine their
photodynamic activity.
2
