Spectral Studies of a Novel Photosensitizer Complex for PhotodynamicTherapy

Introduction: Photodynamic therapy is a safe and low-invasive technology that uses photosensitizers and specific light sources to treat malignant tumors. However, conventional photodynamic therapy faces challenges, such as low photosensitizer uptake by tumors and the tumor microenvironment. To enhance the effectiveness of traditional photodynamic therapy, a nanomaterial-based enzyme-mediated approach was developed. Ceruloplasmin (CP), a coppercontaining protein involved in angiogenesis and antitumor activity, was combined with Fotoditazin® as a photosensitizer and loaded into inorganic particles as carriers. Methods: For photosensitizer complex encapsulation, initial calcium carbonate (vaterite) particles were prepared by the coprecipitation method and characterized using scanning electron microscopy. The obtained particles were loaded with photosensitizer-based complex (Fotoditazin® + CP) using freezing-induced loading. The extinction and fluorescence spectra of the complex were measured. To explore (Fotoditazin® + CP) complex photobleaching dynamics, UV/Vis spectrophotometry was used. For the possible application of obtained particles as a drug delivery system (Fotoditazin® + CP), complex release was also investigated. Results: Our results demonstrate that а Fotoditazin® complex with ceruloplasmin was successfully obtained in 0.9% NaCl under pH 7.4-6.2 conditions. It was revealed that irradiation of the obtained complex with a Red-Blue LED for 30 minutes in 0.9% NaCl at pH 7.4-6.2 causes photobleaching without destroying the complex. Furthermore, to prepare a controlled drug delivery system, we synthesized vaterite particles as carriers and loaded them with the obtained complex. It was found that 86.94% of Fotoditazin® in the complex with ceruloplasmin was loaded into vaterite microparticles. Moreover, the complete release of Fotoditazin® encapsulated as a complex with ceruloplasmin from vaterite microparticles incubated in water occurred after 48 hours. Discussion: The study demonstrates that the (Fotoditazin® + CP) complex interacts with proteins and shows pH-sensitive behavior, making it effective for targeted drug delivery in photodynamic therapy. Calcium carbonate-based microparticles, due to their biocompatibility and responsiveness to acidic environments, are promising carriers for controlled release of photosensitizers in tumor tissues. Conclusion: This study demonstrated a new photosensitizer-based complex with ceruloplasmin to improve photodynamic therapy efficacy. The obtained complex was loaded into vaterite carriers using freezing-induced loading. The application of such drug delivery systems aims to improve the targeted release of photosensitizers at therapeutic doses with minimal side effects.