ABSTRACT
Photodynamic 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.
ABSTRACT
Myoglobin combined with human serum albumin (Mb-HSA) can be produced using yeast Pichia pastoris as a host strain, with secretion into the culture medium. This Mb-HSA fusion protein possesses identical O2 binding affinity to that of naked Mb. The Mb unit is reconstituted with a zinc(II) protoporphyrin IX, yielding (zinc substituted Mb)-HSA, ZnMb-HSA. The photophysical property and singlet O2 generation ability of ZnMb-HSA are equivalent to those of ZnMb. In vitro cell experiments revealed that ZnMb-HSA acts as a superior photosensitizer for photodynamic cancer therapy. It is noteworthy that ZnMb-HSA shows long circulation lifetime inâ vivo.
