Combining Water‐Soluble Porphyrin and Phthalocyanine Photosensitizers With Doxorubicin Improves the Efficacy of Chemo‐Photodynamic Therapy Against DMBA‐Induced Breast Carcinoma

Breast cancer ranks as the second most widespread form of cancer globally. Currently, combination therapy is being actively employed in clinical practice to augment the efficiency of anticancer treatment. Hence, the objective of this study was to assess the therapeutic efficacy of a combination of femtosecond laser-based photodynamic therapy (PDT) utilizing two distinct photosensitizers (PSs), zinc phthalocyanine tetrasulfonate (ZnPcS₄) and α,β,χ,δ porphyrin-Tetrakis (1-methylpyridinium-4-yl) p-Toluenesulfonate porphyrin (TMPyP) in conjunction with doxorubicin chemotherapeutic agent, on mammary carcinomas experimentally induced in female mice using 7,12-dimethylbenz[a] anthracene (DMBA). Our results showed the efficiency of the combined therapy for promoting tissue apoptosis and necrosis as evidenced by histopathological observations and the noticeable reduction of Bcl-2 and Ki-67 expression. Moreover, there was a reduction in serum levels of the carcinoma antigen CA15-3 and transforming growth factor beta (TGF-β). Co-treatment of doxorubicin with ZnPcS₄-PDT or TMPyP-PDT or a combination of both resulted in a decrease in the expression of epidermal growth factor receptor (EGFR) and its downstream oncogenes NRAS, NF-κB, mTERT, and c-Myc, and an increase in the expression of the caspase-3 apoptotic gene. These results validate the therapeutic potential of combining doxorubicin with PDT, highlighting the potential of this co-treatment strategy as a promising alternative for enhancing existing anticancer approaches.