Photodynamic therapy (PDT) is a modern minimally invasive method of treating oncological diseases. PDT is based on the use of a photosensitizer (PS), a light-sensitive drug that triggers a chain of photochemical reactions leading to the formation of cytotoxic singlet oxygen and/or reactive oxygen species that destroy tumor cells. An important challenge for further progress in PDT is to overcome the limitations associated with PS delivery and oxygen availability in tumors. Therefore, the development of drug delivery systems based on hemoglobin (Hb) has attracted increasing attention. Hb serves as a delivery system for both PS and molecular oxygen in hypoxic tumor cells.

Here, we synthesized Zn-substituted hemoglobin (ZnHb), in which heme was replaced by Zn-protoporphyrin IX (ZnPP), an effective PS. The photophysical properties and singlet oxygen generation by ZnPP in a complex with Hb were studied. It was shown that interaction of ZnPP with Hb leads to the increase in the PS's triplet state lifetime by more than 10 times, which is associated with a significant decrease in the access of molecular oxygen to ZnPP embedded in the heme pocket. ZnPP in the complex with Hb does not lose the ability to generate singlet oxygen. It was found that laser irradiation causes photodestruction of ZnHb, with ZnPP not leaving the heme pocket at a pH of 7.2. The release of ZnPP from the protein occurs with an increase in the acidity of the medium, which leads to the aggregation of ZnPP and a significant decrease in singlet oxygen generation.