FOLIC ACID-FUNCTIONALIZED GOLD AND SILVER NANOPARTICLES: THEIR CYTOTOXIC EFFECT ON CANCEROUS MYELOID CELLS WITH MICROWAVE IRRADIATION

Abstract

Introduction: Metal nanoparticles such as gold and silver nanoparticles have attracted much interest during the last decades for their special chemical and physical properties. Gold and silver nanoparticles can be functionalized with active biologic moieties like antibodies, drugs and chemicals, enabling them to react with specific cells. Furthermore, penetration and cytotoxic effects of nanoparticles can be increased by electromagnetic waves such as infrared, ultraviolet, radiofrequency and microwave. Aim: The aim of this study was to evaluate the rate of cell cytotoxicity induced by folic acid-functionalized gold and silver nanoparticles with and without microwave irradiation on cancer cells from patients with acute myeloid leukemia (AML). Method: Patients with known AML (M1, M2, M3 and M4), all recently diagnosed by histopathology, special stains and immunohistochemistry, and 4 normal persons were enrolled in the study. The blood mononuclear cell fraction was separated, so that the final concentration of neoplastic myeloid cells and normal mononuclear cells in each tube was adjusted to about 400 cells/μL. For preparation of folate-functionalized gold and silver nanoparticles, folic acid was dissolved in deionized water, added to 1 mM HAuCl4 and 1 mM AgNO3 solution, and incubated at 50°C for 8 h. Scanning electron micrographs, ultraviolet-visible spectrophotometer and Fourier transform infrared (FTIR) were used for confirmation of the synthesis of functionalized nanoparticles. After preparation, nanoparticles were added to cancerous and normal cell suspensions, and then incubated at 37°C for 1 h. Another experiment was carried out in the same way but with exposure to microwave irradiation for 10 s so that its temperature reached at 50°C, and then incubated at 37°C for 1 h, after which cell cytotoxicity was evaluated with MTT test. All of the tests were duplicated, and paired t-test was used to compare the mean absorbance read-out in each of the above-mentioned groups of wells. Results: The sizes of functionalized gold and silver nanoparticles were approximately 25 nm to 32 nm. After synthesis of functionalized nanoparticles, the tubes containing HAuCl4 turned to red color, and the peak absorbance for gold nanoparticles was at 520 nm. For AgNo3 , it turned to yellow color with a peak absorbance at 420 nm. FTIR test showed connection of folic acid moieties to gold and silver surfaces. This study showed that functionalized gold nanoparticles were more toxic than functionalized silver nanoparticles on cancer and normal cells. Also, microwave irradiation was more synergic with functionalized gold nanoparticles. Furthermore, the most effectiveness score was 2.87 for functionalized silver nanoparticles without microwave irradiation and the minimum effectiveness score was 2.20 for functionalized silver nanoparticles with microwave. Conclusion: This study clearly demonstrated that although functionalized gold nanoparticles have high toxicity to cells, but silver nanoparticles without microwave irradiation are more effective because of less cytotoxic effect on normal cells.