Immunogenic necroptosis in the anti-tumor photodynamic action of BAM-SiPc, a silicon(IV) phthalocyanine-based photosensitizer.

Abstract

Photodynamic therapy (PDT) is an anti-tumor modality which employs three individually non-toxic substances, including photosensitizer, light and oxygen, to produce a toxic effect. Besides causing damage to blood vessels that supply oxygen and nutrients to the tumor and killing the tumor by a direct cytotoxic effect, PDT has also been known to trigger an anti-tumor immune response. For instance, our previous study showed that PDT with BAM-SiPc, a silicon(IV) phthalocyanine based-photosensitizer, can not only eradicate the mouse CT26 tumor cells in a Balb/c mouse model, but also protect the mice against further re-challenge of the tumor cells through an immunomodulatory mechanism. To understand more about the immune effect, the biochemical actions of BAM-SiPc-PDT on CT26 cells were studied in the in vitro system. It was confirmed that the PDT treatment could induce immunogenic necroptosis in the tumor cells. Upon treatment, different damage-associated molecular patterns were exposed onto the cell surface or released from the cells. Among them, calreticulin was found to translocate to the cell membrane through a pathway similar to that in chemotherapy. The activation of immune response was also demonstrated by an increase in the expression of different chemokines.