Redox-Sensitive Fluorescent Nanoparticles for Biovisualization of Malignant Tumors.

Abstract

Application of fluorescent redox-sensitive nanoparticles in current biomedicine ensures high sensitivity and accuracy of biovisualization. Nanoparticles are potent as they can long circulate in the blood, where the level of glutathione is relatively low, and are destroyed in tumor cells, releasing loaded dyes or drugs. The aim of the study was to develop new nanoparticles based on trithiocyanuric acid for biovisualization of malignant tumors and study capabilities of the developed nanoparticles.

Materials and methods: Nanoparticles were obtained by polycondensation of trithiocyanuric acid using iodine. Scanning and transmission electron microscopy was used for their characterization, the loading of fluorescent dyes was assessed by means of spectrophotometry. Confocal laser scanning microscopy was applied to study the impact of nanoparticles on the viability of the 4T1 and A549 cell lines as well as their interaction with cells. The distribution of nanoparticles in tissues and organs of BALB/c model mice with grafted tumors was performed using fluorescence visualization.

Results: According to scanning microscopy, the size of the synthesized particles reached 100±20 nm. The adsorption isotherm demonstrated that adsorption of 0.27 mg of the RhB fluorescent dye per 1 mg of nanoparticles could be achieved. Enhanced release of the packed fluorescent dye was seen in the presence of glutathione and acetylcysteine. The particles did not significantly affect the viability of 4T1 and A549 cells. After intratumoral administration, they ensured a more intense fluorescent signal in the tumor area compared to a regular fluorescent dye solution.

Conclusion: The developed system of trithiocyanuric-acid-based nanoparticles demonstrated high efficiency in biovisualization of malignant tumors and has a potential for targeted delivery of treatment agents.