O21 - Photodynamic Therapy with Novel Third-Generation Photosensitizer Combined with Chemotherapy to Treat Triple Negative Breast Cancer In Vitro

Introduction: : Photodynamic therapy (PDT) is a minimally invasive therapeutic option for cancer patients. PDT is especially promising for the treatment of triple negative breast cancer (TNBC) which comprises of 15% of all breast cancers. PDT focuses anti-cancer effects on a tumor as only specific wavelengths of light activate injected cancer killing photosensitizers (PS) molecules. The third-generation PS used in this study improves upon earlier PS renditions as it combines a second-generation PS, temoporfin (m-THPC) with a polymer carrier, dextran-grafted-polyacrylamide (D-g-PAA), and gold nanoparticles (AuNP). The goal of this study was to improve upon the efficacy of PDT while reducing IC50 concentration required for traditional chemotherapy when used in combination therapy.

Materials and

Methods: : Cell used in this study included human derived TNBC cell lines, MDA-MB-231 and MDA-MB-468, mouse derived TNBC cell line, 4T1, human derived epithelial mammary cell line, MCF10A, and mouse derived epithelial mammary cell line, NMuMG. D-g-PAA synthesized with AuNP was compounded with m-THPC before application to cells. Chemotherapy drugs used in this study were Adriamycin, Cytoxan, and Taxol. PDT was performed prior to 24-hour chemotherapy application. An ideal concentration of PS and chemotherapies were determined separately. Concentrations of PS that significantly reduced TNBC numbers were used for combination therapy. The effectiveness of the combination therapy was further verified by comparison of MTT and TUNEL assays.

Results, Conclusions, and Discussions:: We found that there is a reduction in the IC50 concentration of traditional TNBC chemotherapy when used in combination with PDT. There is also increased TNBC cell death with the PDT + chemotherapy combination. Along with reduced TNBC cell numbers, there was also a reduction of TNBC cell metabolism based on MTT assays and an increase of TNBC DNA fractionization indicating induction of apoptosis after combination therapy. In conclusion, effective treatment of TNBC is possible with lower than IC50 concentrations of chemotherapy when used in combination with PDT that utilizes a novel third-generation PS.

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