A photocontrollable conjugate of a natural chlorin and a chemotherapeutic agent for combined photodynamic therapy.

PDT is known as a non-invasive technique for the treatment of tumors of epithelial tissues. One of the main directions in the development of PDT methods is to increase their cytotoxicity. For this purpose, a combined therapy strategy is being implemented, which consists of the simultaneous use of a photosensitizer and cytotoxic agent [1]. Doxorubicin is one of the most commonly used chemotherapeutic agents. In order to reduce its off-target toxicity and implement the principle of combination therapy, guided delivery systems need to be developed [2]. Light is a convenient external stimulus, and conjugates of therapeutic agents through photocleavable linkers have been shown to be effective for combined PDT [3].

In our work, we obtained a conjugate of the derivative of natural chlorin, anthracycline antibiotic doxorubicin and a photocleavable linker. The mechanism of photochemical destruction was studied both experimentally using light irradiation, UV-Vis spectrophotometry, and fluorescence spectroscopy, as well as computationally using density functional theory (DFT) calculations. We conducted biological tests on a human breast cancer cell line MCF-7 and tried to interpret the results obtained in vitro using in silico docking methods.

The work was carried out with the support of the Ministry of Science and Higher Education of the Russian Federation within the framework of the state assignment, research topic project № FSFZ-2025-0020.

1) Grin, Mikhail, et al. "Advantages of combined photodynamic therapy in the treatment of oncological diseases." Biophysical Reviews 14.4 (2022): 941-963.

2) Chen, Pinggui, et al. "Porphyrin-based covalent organic frameworks as doxorubicin delivery system for chemo-photodynamic synergistic therapy of tumors." Photodiagnosis and Photodynamic Therapy 46 (2024): 104063.

3) Johan, Audrey Nathania, and Yi Li. "Development of photoremovable linkers as a novel strategy to improve the pharmacokinetics of drug conjugates and their potential application in antibody–drug conjugates for cancer therapy." Pharmaceuticals 15.6 (2022): 655.