Vascular Shutdown and Pro-inflammatory Cytokine Expression in Breast Cancer Tumors after Photodynamic Therapy Mediated by Nano-sized Liposomes Containing Aluminium-Chloride-Phthalocyanine

Abstract

Breast cancer is the most prevalent solid tumor worldwide, being the second most common cause of death in women. Treatments recommended for breast cancer include both local and regional protocols such as surgery and radiotherapy, and systemic procedures, such as chemotherapy and hormonal therapies. In most of them, there is much functional impairment and low selectivity for tumor, leading to immunosuppression. Alternatively, some new protocols such as Photodynamic therapy (PDT) has been proposed as a therapeutic option for breast cancer management. One of the promising features related to PDT is immune activation against tumor cells. Thus, considering the importance of immunological activation against tumor cells after PDT, the aim of this study was to evaluate the expression of local and systemic inflammatory cytokines in breast cancer-bearing mice after PDT application, mediated by the photosensitizer aluminium-chlorine-phtalocyanine (AlClPc) in liposomal formulation (Lipo-AlClPc). In addition, we evaluate the efficacy of this PDT protocol in the treatment of murine mammary carcinoma cell line – 4T1 in in vitro and in vivo experimental models. It could be observed in the present study that PDT mediated by local application of Lipo- AlClPc in the treatment of breast cancer in Balb / c mice acted by multiple mechanisms, including the induction of cell death by necrosis and due to direct oxidative damage to tumor cells and vascular shutdown. All these events contributed to the expression of inflammatory cytokines, resulting in a subsequent anti-tumor inflammatory response. In conclusion, PDT mediated by Lipo-AlClPc is capable of activating an inflammatory response, providing support to be used at least as an adjunct therapy to surgical treatments, allowing greater tumor control for long periods and, possibly, greater control of metastatic foci.