Zinc Substituted Myoglobin−Albumin Fusion Protein: A Photosensitizer for Cancer Therapy

• Published in: Chemistry : a European journal 2023-04, Vol.29 (22), p.e202203952-n/a
• Main Authors: Yamada, Taiga, Morita, Yoshitsugu, Takada, Ryoya, Funamoto, Mizuki, Okamoto, Wataru, Kohno, Mitsutomo, Komatsu, Teruyuki
• Format: Article
• Language: English
• Subjects: Albumin; Albumins; Cancer; Cancer therapies; Cell culture; Chemistry; circulation lifetime; Fusion protein; Human serum albumin; Humans; Myoglobin - chemistry; Myoglobins; Neoplasms - drug therapy; photodynamic therapy; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Proteins; Protoporphyrin; Protoporphyrin IX; reconstituted myoglobin; Serum albumin; singlet oxygen; Substitutes; Yeasts; Zinc; Zinc - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202203952

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 in vivo. Myoglobin combined with human serum albumin, Mb‐HSA, was prepared using a yeast host cell with secretion into the culture medium. The heme of Mb‐HSA was replaced with a zinc protoporphyrin IX, yielding ZnMb‐HSA. This fluorescent fusion protein showed a superior activity of photodynamic cancer therapy in vitro. Its blood circulation half‐life was 11‐fold longer than free ZnMb in vivo.