Synthesis, characterization and comparison of the properties of systems based on dumbbell-shaped magnetite-gold nanoparticles, cyanine florophore and a photosensitizer of the bacteriopheophorbide series for theranostics of oncological diseasesтезисы доклада
Аннотация:The problem of cancer therapy is acute for scientists and doctors around the world. The frequency of cases of cancer diagnosis increases every year. On average, ten million people worldwide fall ill each year. This is associated both with the improvement of diagnostic methods and with the influence of factors that provoke such diseases. One of the most interesting objects from the point of view of application in biomedicineare hybrid structures based on magnetic nanoparticles (NPs) and noble metal NPs, which make it possible to simultaneously introduce two types of ligands onto the surface of NPs for their further use. This type of dumbbell-shaped NP opens up the possibility of their functionalization for further use in cancer photodynamic therapy (PDT) and fluorescence diagnostics (FD) [a combination of a photosensitizer (PS) for therapyand a fluorophore (FP) for platform detection]. Due to the conjugation of PS and FP at an optimal distance, obviously greater than the typical values of the Förster radius, which will avoid the FRET effect. However, the question also arises about the need to create a more complex Fe3O4–Au/PS/FP system or a mixture of Fe3O4–Au/PS + Fe3O4–Au/FP.MethodsThe goal of this work was to synthesize and compare the properties of Fe3O4-Au/PS/FP systems with a mixture of Fe3O4- Au/PS + Fe3O4-Au/FP conjugates. The previously synthesized hybrid magnetite and gold NPs had sizes of Fe3O4 10.8 ± 1.5 nm and Au 4.4 ± 0.8 nm (according to TEM data). The NPs were doubly modified with 3,4-dihydroxyphenylacetic acid(DOPAC) for subsequent coating with stabilizing polyethylene glycol (PEG) using the carbodiimide method. Since it is necessary to combine two different substances (PS and FP) in one system, Fe3O4-Au NPs stabilized) were used as a ‘link’. Modification of DOPAC and PEG NPs with subsequent activation of EDC/NHS allows effective attachment of PS to the magnetic surface of NPs in a two-phase system (water–DMSO).The hydrodynamic size of the Fe3O4-Au/PS/FP system was 35.9 nm, the Fe3O4-Au/PS + Fe3O4-Au/FP mixture was 36.4 nm, respectively (dynamic light scattering method). For the Fe3O4– Au/PS/FP systems under study, as well as the Fe3O4–Au/PS + Fe3O4–Au/FP mixture, absorption maxima corresponding to solutions of pure PS and FP were recorded by spectroscopy, which confirms the efficiency of their conjugation. For the mixture Fe3O4–Au/PS + Fe3O4–Au/FP, a resonant transfer of fluorescence energy was discovered: upon excitation of the FP with a wavelength of 660 nm, additional emission of the PS inthe region of 770 nm.ResultsIt was shown that Fe3O4–Au/PS/FP systems and a mixture of Fe3O4–Au/PS and Fe3O4–Au/FP could be internalized by CT26 colon cancer cells with preservation of optical properties.Studies of the cytotoxicity of the systems on CT26 cell lines showed that the systems do not have dark toxicity in the studied concentration range. Studies of the light toxicity of the systems showed photo induced activity of the systems.Phototoxicity studies showed that after 4 h of incubation, the IC50 value for the Fe3O4–Au/PS + Fe3O4–Au/FP mixture was 1763 ± 15 ng/mL, and for Fe3O4–Au/PS/FP it was 483 ± 7 ng/mL.ConclusionsBased on the obtained comparative results, we can talk about higher efficiency of Fe3O4–Au/FS/FP for all parameters studied. However, in vivo studies are planned in the near future to finalize the findings.
