In Vivo Photodynamic Therapy With A Lipophilic Zinc(Ii) Phthalocyanine Inhibits Colorectal Cancer And Induces A Th1/Cd8 Antitumor Immune Response

Background and Objectives Photodynamic therapy (PDT) is an antitumor procedure clinically approved for the treatment of different cancer types. Despite strong efforts and promising results in this field, PDT has not yet been approved by any regulatory authority for the treatment of colorectal cancer, one of the most prevalent gastrointestinal tumors. In the search of novel therapeutic strategies, we examined thein vivoeffect of PDT with a lipophilic phthalocyanine (Pc9) encapsulated into polymeric poloxamine micelles (T1107) in a murine colon carcinoma model. Study Design/Materials and Methods In vivo assays were performed with BALB/c mice challenged with CT26 cells. Pc9 tumor uptake was evaluated with anin vivoimaging system. Immunofluorescence, western blot, and flow cytometry assays were carried out to characterize the activation of apoptosis and an antitumor immune response. Results Pc9-T1107 effectively delayed tumor growth and prolonged mice survival, without generating systemic or tissue-specific toxicity. The induction of an apoptotic response was characterized by a decrease in the expression levels of Bcl-X-L, Bcl-2, procaspase 3, full length Bid, a significant increment in the amount of active caspase-3 and the detection of PARP-1 cleavage. Infiltration of CD8(+)CD107a(+)T cells and higher levels of interferon-gamma and tumor necrosis factor-alpha were also found in PDT-treated tumors. Conclusions Pc9-T1107 PDT treatment reduced tumor growth, inducing an apoptotic cell death and activating an immune response. Lasers Surg. Med. (c) 2020 Wiley Periodicals LLC