Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Area of Science:

• Biochemistry
• Oncology
• Photomedicine

Background:

• Photodynamic therapy (PDT) is a promising cancer treatment that utilizes photosensitizers and light to generate reactive oxygen species (ROS), causing tumor cell death and microvascular injury.
• Developing new photosensitizers is crucial for enhancing PDT efficacy and minimizing side effects.
• Oxidative stress, a key mediator of PDT, influences various cellular and molecular pathways within the tumor microenvironment.

Purpose of the Study:

• To evaluate the effects of PDT using 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on biochemical markers and enzyme activity in Walker 256 carcinosarcoma tumors.
• To correlate the observed biochemical changes with histological alterations in the tumor tissue following PDT.
• To elucidate the role of ROS in mediating the therapeutic effects of PDT with TMPP and ZnTMPP.

Main Methods:

• Walker 256 carcinosarcoma-bearing Wistar rats were randomly assigned to five groups: ZnTMPP+irradiation, TMPP+irradiation, 5-aminolevulinic acid (5-ALA)+irradiation, control (no treatment), and irradiation only.
• Tumors were irradiated with red light (685 nm) 24 hours after drug administration.
• Tumor tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), and cytokines (TNF-α) were measured.
• Activity of caspase-3 and matrix metalloproteinases (MMP-2 and -9) were assessed.
• Histological alterations were analyzed and correlated with biochemical findings using Spearman correlation.

Main Results:

• PDT with ZnTMPP and TMPP significantly increased tumor levels of malondialdehyde (MDA) and TNF-α compared to controls.
• Elevated caspase-3 activity and activation of MMP-2 were observed in tumors treated with TMPP and ZnTMPP.
• These biochemical and enzymatic changes showed a significant correlation with observed histological alterations in the tumor tissue.
• PDT treatments, particularly with ZnTMPP, demonstrated a marked increase in MDA and TNF-α levels.

Conclusions:

• PDT with TMPP and ZnTMPP effectively induces oxidative stress, evidenced by increased MDA levels, which contributes to tumor cell damage and apoptosis.
• The observed increase in caspase-3 activity and MMP-2 activation suggests that PDT triggers programmed cell death and matrix degradation pathways.
• PDT with these novel photosensitizers activates the innate immune system, highlighting their potential as effective therapeutic agents in cancer treatment.
• The findings underscore the critical role of ROS in mediating the anti-tumor effects of PDT.