Synthesis, Characterization, and Biological Evaluation of a Porphyrin-Based Photosensitizer and Its Isomer for Effective Photodynamic Therapy against Breast Cancer

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.