Abstract PS4-06-10: A Promising Approach for Hard-to-Treat Breast Cancer: Photodynamic Therapy with ClAlPc Nanoemulsion Against Triple-Negative Cells

Abstract Triple-negative breast cancer is a highly aggressive subtype with the poorest prognosis among breast cancers. It is defined by the absence of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2), limiting the effectiveness of conventional hormone-based therapies. Around 20% of the 2.3 million annual breast cancer cases are triple-negative, and this subtype is linked to high metastasis and mortality rates. Its molecular heterogeneity and therapeutic resistance highlight the urgent need for alternative treatment strategies. Photodynamic therapy is a promising, minimally invasive technique already employed in Brazil’s public health system (SUS) for the treatment of basal cell carcinoma. It relies on the activation of a photosensitizer (PS) by a specific light source, leading to the generation of reactive oxygen species (ROS) that trigger oxidative stress, cell death, and immune response activation. This in vitro study assessed the cytotoxicity of photodynamic therapy using a nanoemulsion containing chloroaluminum phthalocyanine (ClAlPc/Ne) in breast cancer cell lines exposed to varying PS concentrations and light doses. The MCF-7 and MDA-MB-231 cell lines, representing luminal A and triple-negative breast cancer respectively, were incubated with ClAlPc/Ne for 24 hours before photoactivation, followed by a further 24-hour incubation before metabolic viability analysis using the MTT assay. Three experimental conditions were tested: (I) nanoemulsion without PS, (II) ClAlPc/Ne without irradiation, and (III) photoactivated ClAlPc/Ne. PS concentrations ranged from 0.01 µM to 2.0 µM, with light doses from 1 J/cm2 to 16 J/cm2. Absorbance was measured at 545 nm. Results showed selective phototoxicity of ClAlPc/Ne against the triple-negative breast cancer cell line MDA-MB-231, with IC50 (50% inhibitory concentration) values of 1.96 µM at 1 J/cm2, 0.19 µM at 4 J/cm2, and <0.01 µM at 16 J/cm2. In contrast, MCF-7 cells demonstrated greater resistance, with IC50 values of >2.0 µM at 1 J/cm2, 0.14 µM at 4 J/cm2, and <0.06 µM at 16 J/cm2. These findings indicate that phototoxicity is dose-dependent and more pronounced in triple-negative breast cancer cells. The differential response between cell lines suggests that triple-negative breast cancer may be more sensitive to oxidative stress induced by photodynamic therapy. These findings reinforce the importance of molecular profiling in guiding treatment decisions and support the potential of photodynamic therapy as a targeted, less invasive approach for hard-to-treat breast cancer subtypes. Citation Format: H. R. Luz, L. P. Franchi, A. C. Tedesco, E. d. Lacerda. A Promising Approach for Hard-to-Treat Breast Cancer: Photodynamic Therapy with ClAlPc Nanoemulsion Against Triple-Negative Cells [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-10.