Detonation nanodiamonds as enhancers of E. coli photodynamic inactivation by phthalocyanines in a high molarity buffer solution.

Antimicrobial therapy, especially inactivation of multi-antibiotic-resistant strains, requires creating new approaches for drug action and targeted delivery in different environmental conditions. In this work, detonation nanodiamonds (DNDs) were used to deliver polycationic zinc phthalocyanines to E. coli cells. It is shown that in aqueous solutions, zinc phthalocyanines with cholinyl peripheral substituents form complexes with negatively charged DND based on electrostatic interactions. About 40-70 phthalocyanine molecules can bind to a single DND particle, depending on the number of charged groups of the dye molecule. During the complex formation, quenching of phthalocyanine fluorescence and a decrease in its ability to generate reactive oxygen species were observed. In the presence of bacterial cells, phthalocyanine left the complex and induced a photodynamic effect, the magnitude of which depended on the phthalocyanine charge, the molarity of the buffer solution, and the stoichiometry of the phthalocyanine-DND complex. It was found that at physiological values of the ionic strength of the solution, the photodynamic effect of phthalocyanine with a charge of 8+ in combination with a DND is higher than that of the initial phthalocyanine. Thus, nanodiamonds are a promising platform for the delivery of photosensitizers in antimicrobial therapy.

Modification by transferrin increases the efficiency of delivery and the photodynamic effect of the quantum dot-phthalocyanine complex on A431 cells.

Hybrid complexes of fluorescent nanoparticles and tetrapyrrole dyes are currently considered as promising third-generation photosensitizers for photodynamic therapy, including cancer treatment. Using nanoparticles as a platform for delivery of photosensitizers to target cells can increase the efficiency of photodynamic action. In this work, we synthesized a complex of polymer-coated CdSe/ZnS quantum dots, substituted phthalocyanines and human transferrin. Such complexes effectively enter human epidermoid carcinoma cells (A431) due to transferrin-mediated endocytosis and are localized in the perinuclear compartment. We observed an efficient excitation energy transfer from the quantum dot to phthalocyanine in the cells, which indicates stability of the complex upon its internalization. It was shown that the photodynamic activity of hybrid complexes covalently bonded to transferrin is 15% higher than the activity of unmodified hybrid complexes. Our results confirm the feasibility of using fluorescent nanoparticles to enhance the photodynamic properties of photosensitizers based on tetrapyrrole dyes.