Transport of Zinc‐Phthalocyanine to Cancer Cells Using Myoglobin−Albumin Fusion Protein for Photodynamic Therapy

Abstract

AbstractPhotodynamic therapy (PDT) is a noninvasive approach to cancer treatment, wherein cell death is initiated by singlet oxygen (1O2) production via energy transfer from excited photosensitizers to ground‐state O2. Effective clinical photosensitizers necessitate water solubility for in vivo administration. Hydrophobic dyes, such as phthalocyanines, cannot be used directly as photosensitizers. Herein, we synthesized a myoglobin‐(human serum albumin) fusion protein reconstituted with zinc‐phthalocyanine (ZnPc), termed ZnPcMb‐HSA. The photophysical properties of ZnPcMb‐HSA closely resemble those of ZnPc‐substituted Mb. Notably, ZnPc dissociates from ZnPcMb‐HSA and selectively accumulates within cancer cells, while the protein components remain extracellular. Treatment of four distinct cell lines with ZnPcMb‐HSA, followed by red‐light irradiation, effectively induced apoptosis. The half‐maximal inhibitory concentrations (IC50) against these cancer cell lines ranged between 0.1–0.5 μM. Reconstituted Mb‐HSA emerges as a promising carrier for transporting various water‐insoluble porphyrinoid photosensitizer to target cancer cells in PDT applications.