Interaction and oxidative damage of DVDMS to BSA: a study on the mechanism of photodynamic therapy-induced cell death

Abstract

Photodynamic therapy (PDT) is a promising method for neoplastic and nonneoplastic diseases. In this study, we utilized sinoporphyrin sodium (DVDMS) as a sensitizer combined with light to investigate its cytotoxic effect on different cell lines. For this purpose, we chose bovine serum albumin (BSA) as a model to explore the mechanism of PDT-induced cell death at a molecular level. Our findings indicated that the combined treatment significantly suppressed cell survival. Fluorescence spectroscopy revealed a strong interaction between DVDMS and BSA molecules in aqueous solution, affecting DVDMS’ targeting distribution and metabolism. Spectroscopic analysis and carbonyl content detection indicated that DVDMS-PDT significantly enhanced the damage of BSA at a higher extent than Photofrin II-PDT under similar experimental conditions. Our observations were consistent with the cytotoxicity results. Excessive reactive oxygen species (ROS) were induced by the synergy effect of the sensitizer and light, which played an important role in damaging BSA and tumor cells. These results suggested that the interaction and oxidative damage of protein molecules by DVDMS were the main reasons to cell death and constitute a valuable reference for future DVDMS-PDT investigations.

Focused ultrasound-augmented targeting delivery of nanosonosensitizers from homogenous exosomes for enhanced sonodynamic cancer therapy

“…As shown in Figure 2A-B , the pH and serum concentration of the buffer significantly affected the spectra of DVDMS but not that of EXO-DVDMS, consistent with previous findings on free-DVDMS 44, 45. The fluorescence emission spectrum of free-DVDMS in the presence of serum was a result of the random and unstable interactions between DVDMS and the serum proteins that stabilize the physical properties of the former.…”

“…Under serum-free with no US, the red fluorescence signals of DVDMS co-localized with the green fluorescence signals of MitoTracker Green (MTG), and partially with the green signals of ER (endoplasmic reticulum) tracker but not with that of LysoTracker Green (LTG), indicating that DVDMS mainly accumulated in the mitochondria (Figure S11) . However, in physiological condition with serum, Free-DVDMS largely co-localized with LTG (Figure 5) , indicating an altered intracellular route via the lysosomes, due to aggregation of DVDMS and proteins 44. For EXO-DVDMS also, DVDMS was localized in the endo/lysosomes, indicating cellular uptake via endocytosis, consistent with the major cellular internalization mode of exosomes 51.…”

“…In our previous studies, we observed a strong spontaneous interaction between DVDMS and proteins (e.g. BSA) on at least one independent binding site in aqueous solution 44. Therefore, we hypothesize that the new peak could be due to the two sterically hindered porphyrin rings of DVDMS interacting with the exosomal proteins, which results in one surface-attached and one free porphyrin ring 37, 38.…”

“…The interactions between porphyrins and the endogenous biomacromolecules are unavoidable, and can affect the physical and chemical properties of sonosensitizers and thus decrease the SDT efficacy 44. For example, recent spectroscopic studies show poor stability of DVDMS at acidic pH 45.…”

Selective photocytotoxicity of anthrols on cancer stem-like cells: The effect of quinone methides or reactive oxygen species

“…For example, PS can localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes[52,53]. It is therefore important to confirm the target biomolecules and select the appropriate sensitizers relevant for tumor therapy.Interaction and damaging of biological macromolecules became interesting approach in different cancer therapies[54].A promising group of phototherapeutic agents are reactive intermediates -quinone methides (QMs). It is well established that QMs react with biologically important molecules, typically with nucleic acids, but also with amino acids and proteins, particularly with cysteine residues[18].…”