Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine

摘要

Photodynamic therapy (PDT) is a promising method for the localized treatment of solid tumors. In order to enhance the efficacy of PDT, we have recently developed a novel class of photosensitizer formulation, i.e., the dendrimer phthalocyanine (DPc)-encapsulated polymeric micelle (DPc/m). The DPc/m induced efficient and unprecedentedly rapid cell death accompanied by characteristic morphological changes such as blebbing of cell membranes, when the cells were photoirradiated using a low power halogen lamp or a high power diode laser. The fluorescent microscopic observation using organelle-specific dyes demonstrated that DPc/m might accumulate in the endo-/lysosomes; however, upon photoirradiation, DPc/m might be promptly released into the cytoplasm and photodamage the mitochondria, which may account for the enhanced photocytotoxicity of DPc/m. This study also demonstrated that DPc/m showed significantly higher in vivo PDT efficacy than clinically used Photofrin (R) (polyhematoporphyrin esters, PHE) in mice bearing human lung adenocarcinoma A549 cells. Furthermore, the DPc/m-treated mice did not show skin phototoxiciy, which was apparently observed for the PHE-treated mice, under the tested conditions. These results strongly suggest the usefulness of DPc/m in clinical PDT.