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

Abstract

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.

Photodynamic therapy in cancer treatment - an update review

“…PS localization within or on the cell surface is critical to determining the mode of cell death induction and thus the cellular response to photodamage [38,52,53] . Therefore, precise understanding of the preferential subcellular site of PS accumulation is important in order to determine its cytotoxic potential when used in PDT [38,54] . PS uptake by the tumorigenic cells as well as its preferential intracellular site depends on chemical characteristics of each compound.…”

Poly(Lactide‐Co‐Glycolide) Nanoparticles Co‐Loaded with Chlorophyllin and Quantum Dots as Photodynamic Therapy Agents

“…However, solubility, aggregation, and suboptimal body clearance lead to suboptimal therapeutic effect in most cases . Additionally, the need to use wavelengths in the visible range further limits clinical translation.…”

“…[6,7] However, solubility, aggregation, and suboptimal body clearance lead to suboptimal therapeutic effect in most cases. [8] Additionally, the need to use wavelengths in the visible range further limits clinical translation. Although several investigations have been carried out on the use of two-photon irradiation, [9] most of the reported sensitizers have low two-photon crosssections (< 30 GM).…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…The main advantages of porphyrins as PSs in PDT include 1) aromatic stability; 2) efficient absorption of visible red light; 3) high yield of active oxygen; 4) easily functional modification and structural diversity; and 5) long triplet state lifetime and minimal dark toxicity 3,12,14 . Several PSs, such as Photofrin V R , 5,10,15,20-tetrakis(3-hydroxyphenyl)chlorin (Foscan V R ), and 3-(1-hexyloxyethyl)-3-divinylpyropheophorbide (Photochlor V R ) 15 , have been approved for the treatment of various cancers (Figure 1) 16,17 .…”

“…Obviously, any potential PS agent used in PDT should meet the following requirements: 1) should be a single compound with tuneable amphiphilicity, high purity and satisfying yield through mature synthetic methodology 10,16 ; 2) have acceptable dark toxicity; 3) induce high yields of 1 O 2 and reasonable fluorescence quantum yields; 4) have high tumour selectivity and exhibit rapid accumulation and long retention targeting of tumour tissues 18 ; 5) should efficiently absorb red or far-red light to penetrate tissues; 6) show no excessive aggregation in biological environments resulting in a reduction in its photochemical efficiency; and 7) exhibit rapid pharmacokinetic elimination from the patient 11,19 .…”