A
photosensitizer with high
phototoxicity, low dark toxicity, and good water solubility is crucial for effective
photodynamic therapy (
PDT). In this study, a novel class of
porphyrin-based water-soluble derivative and its isomers, named photohexer-1 (P-1) and photohexer-2 (P-2), were synthesized and investigated for anticancer activity. Both of the isomers, P-1 and
P-2, could be utilized as potential sensitizers for
PDT not only owing to their definite constituents but predominantly due to their good absorption in the phototherapeutic window and high generation of intracellular ROS. Therein,
P-2 exhibited stronger
phototoxicity against
breast cancer cells with weaker dark toxicity than P-1; however, both P-1 and
P-2 were highly phototoxic as compared to their homologous compound,
hematoporphyrin monomethyl ether (HMME). These findings were consistent with the antitumor efficacy in vivo. Moreover, P-1 and
P-2 could both effectively localize in multiple subcellular organelles, triggering increased cellular apoptosis or
necrosis under
laser irradiation as compared to HMME. In conclusion, the findings of the study suggest that the two highly water-soluble
porphyrin derivatives may serve as promising putative
photosensitizers for improving the therapeutic efficiency of
PDT.