Interação do azul de metileno-naftil-metil-piperazina com lipídio, proteína e células de câncer de pulmão: implicações para Terapia Fotodinâmica

Abstract

Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer treatments due to its selectivity and lower systemic toxicity. In this context, this study aimed to investigate the photochemical and biological properties of methylene blue derivatives, evaluating their potential application as photosensitizers in the treatment of lung cancer. Methylene blue (MB), its derivative containing a naphthyl-methyl-piperazine group (MB-NMP), and a synthesis intermediate (MB-I) were studied, with emphasis on the relationship between lipophilicity, interaction with biomolecules, and photodynamic activity. Initially, the photodegradation of the compounds under irradiation with red LED (λ = 633 nm) was evaluated, observing lower photodynamic stability for MB and MB-NMP compared to the intermediate AM-I. Lipophilicity was determined using the partition coefficient (LogP), showing a predominantly hydrophilic character for AM-NMP (LogP = -0.7 ± 0.4) and AM (LogP = -1.4 ± 0.3), although the derivative had a slightly higher lipophilicity than its precursor. Liposome binding assays corroborated this result, demonstrating a greater affinity of AM-NMP for lipid systems. The interaction with bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, revealing binding constants on the order of 10³–10⁵ M⁻¹ and an approximate stoichiometry of 1:1, indicating moderate interaction and potential plasma transport capacity. Furthermore, photo-oxidation of BSA showed a faster decrease in fluorescence when in the presence of AM, suggesting faster degradation compared to the other compounds. When evaluating the incorporation rate in A549 cells, higher values were observed for AM-NMP, attributed to its greater lipophilicity. In MTT cell viability tests, the compounds did not show significant toxicity in the dark; however, under irradiation, AM and AM-NMP demonstrated significant phototoxic activity, while the intermediate AM-I did not show a satisfactory effect. The results show that structural modifications in methylene blue directly influence its photophysical properties, interaction with biomolecules, and photodynamic activity. The AM-NMP derivative stood out for its greater lipophilicity and cellular incorporation, and with photodynamic efficiency similar to that of AM. Thus, AM-NMP shows promise as a candidate for application in photodynamic therapy in lung cancer cells.