Investigation of the pH-dependent hydrolysis of a chlorin e6 hydrazide derivative as a potential photosensitizer for combined anticancer therapy

Oncological diseases represent a global healthcare challenge, and the development of new effective therapeutic strategies remains a pressing task. Chemotherapy and photodynamic therapy (PDT) are key treatment modalities, however, their application is associated with side effects, systemic toxicity, and the development of drug resistance. In recent years, combined approaches, including the use of pH-sensitive delivery systems, have been actively investigated. The present study was dedicated to the investigation of the pH-dependent hydrolysis of a chlorin e6 hydrazide derivative, acting as a potential photosensitizer (PS) for combined anticancer therapy. Hydrazide fragments, due to their lability in the weakly acidic environment of the tumor microenvironment (pH 4.5-6.0), are promising for the creation of targeted drug delivery systems. The decomposition of the hydrazide fragment was studied spectrophotometrically in an acetate buffer (pH 5.0) over 120 minutes. Spectral changes (bathochromic shift, appearance of a maximum at 688 nm) were recorded, indicating the formation of a protonated precursor compound. A linear dependence of product accumulation on time was obtained, characteristic of zero-order reactions. A high coefficient of determination confirmed the adequacy of the obtained model. This approach ensures controlled release of active components and demonstrates the potential of the developed PS for enhancing PDT efficacy and reducing the systemic toxicity of chemotherapy.