Synthesis and characterization of aminolevulinic acid gold nanoparticles: Photo and sonosensitizer agent for atherosclerosis

Abstract

Photodynamic and sonodynamic therapies (PDT and SDT, respectively) are emerging as new atherosclerosis treatments. The subsequent generation of free radicals by activated photo and sonosensitizers can lead to apoptotic cell death. The use of gold nanoparticles (AuNPs) as the vehicle for a sensitizer delivery improves reactive oxygen species formation and sensitizer performance. In this study gold nanoparticles functionalized with polyethylene glycol (PEG) were synthesized mixing δ-aminolevulinic acid (ALA) with tetrachloroauric (III) acid in milliQ water solution followed by photo reduction with 300W xenon lamp. The synthesized ALA:AuNPs were characterized by UV/vis optical absorption, zeta potential and electron microscopy. The mean particle size of spherical ALA:AuNP was ~ 18 nm, with a polydispersity index of 0.437. Singlet oxygen generation efficiency was measured using the trap molecule 1,3-diphenylisobenzofuran. ALA:AuNPs and DPBF were irradiated with 590 nm LED, or pulse ultrasound irradiation (1 W/cm2 with 1.0 MHz), and consumption of the DPBF was monitored over time by the absorption and emission spectra. The results showed that he gold nanoparticles generate singlet oxygen during light and ultrasound irradiations. THP-1 cells differentiated into macrophages cytotoxicity test were described and was found the half maximal inhibitory concentration (IC50) values ~ 36 nM for ALA:AuNPs. Increase in the fluorescence intensity of PpIX extracted from macrophages incubated with ALA:AuNPs indicating stable encapsulation of ALA into gold nanoparticles and further conversion to PpIX. The potential use of ALA:AuNps as a sensitizer for photo and sonodynamic therapies were investigated. ALA:AuNPs mediated SDT was more effective than PDT. SDT with ALA:AuNPs induced the reduction of macrophage viability in ~ 87,5% in only 2 min. The mechanism underlying SDT-induced apoptosis involves the generation of singlet oxygen. The results indicate that ALA:AuNPs can be used as a novel photo and sonosensitizer for atherosclerosis.