Efeitos citotóxicos e antiproliferativos da terapia fotodinâmica com ftalocianina de alumínio-cloro em modelos in vitro de câncer de mama triplo-negativo

Abstract

Triple-negative breast cancer represents a major therapeutic challenge due to the absence of hormone receptors and HER2 expression, resulting in limited treatment options and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising strategy for treating aggressive neoplasms by activating photosensitizers with specific-wavelength light to generate reactive oxygen species (ROS) capable of inducing cell death. In this study, we evaluated the cytotoxic, antiproliferative, and antimigratory effects of aluminum-chloride phthalocyanine (AlClPc) encapsulated in Pluronic® F-127 micelles in MDA-MB-231 cells, an in vitro model of triple-negative breast cancer. Cells were treated with different concentrations of the AlClPc-Pluronic® F-127 formulation, followed or not by LED light irradiation (670 nm). Cytotoxicity was assessed by MTT and trypan blue assays; proliferative capacity was evaluated by clonogenic assay with crystal violet staining; and cell migration was analyzed using wound healing and transwell assays. Morphological changes associated with cell death were examined microscopically, and mechanisms of cell death were investigated through propidium iodide and annexin V-FITC staining. The results showed that the AlClPc-Pluronic® F-127 formulation exhibited superior photodynamic efficacy compared to free AlClPc, with an IC₅₀ value of 2.31 µM post-irradiation and cell viability above 90% in the absence of light. Lower concentrations (1–2 µM) were more effective than intermediate or higher concentrations, likely due to reduced photosensitizer aggregation. Furthermore, the formulation significantly inhibited colony formation and cell migration following PDT, and induced apoptosis at lower concentrations, transitioning to necrosis at higher concentrations. These findings indicate that the vectorization of AlClPc with Pluronic® F-127 enhances its antitumor effects in triple-negative breast cancer cells, representing a promising nanotechnological approach for the development of safe, selective, and effective targeted therapies.