乳腺癌（BC）是女性最常见的癌症类型，美国新发病例数每年仍在增加。三阴性乳腺癌 (TNBC) 占所有乳腺癌的 15-20%，是一种异质性疾病，由于缺乏雌激素受体 (ER)、孕激素受体 (PR)，被认为是最具侵袭性的乳腺癌类型，以及用于治疗的人表皮生长因子受体 2 (HER2) 表达。传统化疗是治疗 TNBC 的标准方案。毒性和多药耐药性是化疗的主要缺点。 TNBC 缺乏分子靶点和不良预后促使迫切需要发现新的治疗策略以改善患者的临床结果和生活质量。光动力疗法 (PDT) 或光治疗是一种二元抗癌程序，使用光敏剂 (PS)，光敏剂在光激活后产生细胞毒性氧，破坏肿瘤细胞。 PDT 是微创的，可以重复几次，而不会在周围组织中积累显着的毒性。本研究的主要目标是研究体外光动力化疗作为三元联合疗法，使用我们合成的光敏剂（二氯维生素缀合物及其相应的铟络合物）与已知的化疗药物（紫杉醇、阿霉素、顺铂、氟尿嘧啶或甲氨蝶呤）在光存在下进行，并确定最佳条件作为针对 TNBC 增强杀肿瘤作用的临床前研究。我们的结果表明，有效化学光动力学效应的最佳组合涉及二氢硫辛酸-硫辛酸缀合物（InCLA）与紫杉醇共同处理的铟络合物的三元处理，当在纳摩尔浓度下与紫杉醇组合时，其表现出强烈的协同作用。可见光照射。其他含有对 TNBC 具有协同抗肿瘤作用的紫杉醇的三元组合包括二氢卟酚-泛酸 (CPA) 和二氢卟酚-生物素 (CBTN) 缀合物。其他几种含有 InCLA、CBTN 和 CPA 与顺铂、氟尿嘧啶或甲氨蝶呤的三元组合已被确定可产生协同或相加效应。光剂量保持不变，但光敏剂和化疗药物的剂量发生变化，以获得所需效果的最低可能浓度。基于Chou-Talalay方法确定药物组合的协同、相加或拮抗作用，其中InCLA-紫杉醇的组合指数（CI）最低，为0.25。荧光和透射电子显微镜 (TEM) 图像提供了细胞凋亡作为细胞死亡首选模式的证据。我们的研究表明，PDT 与化疗相结合是 TNBC 患者的潜在治疗选择。

Breast cancer (BC) is the most common type of cancer in women and the number of new cases in the US is still increasing each year. Triple-negative breast cancer (TNBC), which comprises 15-20% of all breast cancer, is a heterogeneous disease and is considered the most aggressive type of breast cancer due to the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions for treatments. Traditional chemotherapy is the standard protocol for the treatment of TNBC. Toxicity and multidrug resistance are major drawbacks to chemotherapy. The lack of molecular targets and poor prognosis for TNBC prompts an urgent need to discover novel therapeutic strategies to improve clinical outcomes and quality of life for patients. Photodynamic therapy (PDT) or light treatment is a binary anti-cancer procedure that uses a photosensitizer (PS) that, upon light activation, produces cytotoxic oxygen species, destroying tumor cells. PDT is minimally invasive and can be repeated a few times without accumulating significant toxicity in the surrounding tissues. The primary goal of this study was to investigate in vitro photodynamic chemotherapy as a ternary combination therapy using our synthesized photosensitizers (chlorin-vitamin conjugates and their corresponding indium complexes) co-treated with known chemotherapeutic agents (taxol, doxorubicin, cisplatin, fluorouracil, or methotrexate) in the presence of light and determine the optimum conditions as a pre-clinical study of an enhanced tumoricidal effect against TNBC. Our results indicated that the best combination for an effective chemophotodynamic effect involves a ternary treatment of the indium complex of the chlorin-lipoic acid conjugate (InCLA) co-treated with taxol, which exhibited strong synergism at the nanomolar concentration when combined in the presence of visible light irradiation. Other ternary combinations containing taxol with a synergistic anti-tumor effect against TNBC include chlorin-pantothenic acid (CPA) and chlorin-biotin (CBTN) conjugates. Several other ternary combinations containing InCLA, CBTN, and CPA with either cisplatin, fluorouracil, or methotrexate were identified to generate a synergistic or additive effect. The light dosage remained constant, but the dosages of photosensitizers and chemotherapy drugs were varied to obtain the lowest possible concentration for the desired effect. The synergistic, additive or antagonistic effects of the drug combinations were determined based on the Chou-Talalay method, with InCLA-taxol having the lowest combination index (CI) of 0.25. Fluorescence and transmission electron microscopy (TEM) images provided evidence of apoptosis as the preferred mode of cell death. Our study demonstrated the combination of PDT and chemotherapy as a potential treatment option for TNBC patients.