Submicron vaterite particles, loaded with porphyrazine photosensitizer for photodynamic therapy of bladder carcinoma cells

Abstract

Background and Objectives: Bladder cancer is one of the ten most common cancers causing a high mortality rate. Photodynamic therapy (PDT) is one of the promising ways to treat this disease. To increase the effectiveness of PDT it is necessary to ensure selective delivery of photosensitizer to the tumor. Selective delivery systems such as nano- and microparticles of calcium carbonate in the polymorphic modification of vaterite are of great interest to solve this problem. Therefore, the aim of this study was to investigate submicron particles of vaterite as agents for selective delivery of photosensitizer PzBn on human bladder T24 cell culture. Materials and Methods: Calcium carbonate particles were obtained by mixing equimolar solutions of CaCl2 and Na2CO3 salts in the presence of glycerol. PzBn was immobilized by adsorbing the substance on preliminarily synthesized vaterite particles. The loading efficiency was evaluated using the spectrophotometric method. The experiments were carried out on the T24 human bladder carcinoma cell line. Intracellular localization was assessed using fluorescent laser confocal scanning microscopy. The study of the dynamics of PzBnVp accumulation by cells was carried out by spectrophotometry. Dark toxicity and photodynamic activity were analyzed using the MTT test. Results: The efficiency of loading porphyrazine into vaterite particles is over 9%. It has been shown that PzBnVp is characterized by rather rapid accumulation by T24 cells: the maximum accumulation is recorded already 30 minutes after its addition, after which the intensity of the fluorescence signal remains at a constant level for 5 hours of observation. It has been demonstrated that PzBnVp is characterized by low dark toxicity with high photodynamic activity. Conclusion: The possibility of loading vaterite particles with the photodynamic dye porphyrazine has been demonstrated. A high rate of entry of vaterite particles into the cell and the release of the loaded photosensitizer from particles and its subsequent redistribution over subcellular structures have been shown. The preservation of the photodynamic activity of porphyrazine in the composition of vaterite particles and the absence of dark toxicity in the studied concentration range have been demonstrated. Vaterite particles can be considered as promising agents for the selective delivery of porphyrazine to the tumor in order to increase the efficiency of photodynamic therapy.

Keywords

• photodynamic therapy
• photosensitizer
• vaterite
• porphyrazine
• bladder cancer