Preparation of doxorubicin modified silver nanoparticle and its anti-tumor activity in vitro / 天津医药

ABSTRACT

Objective To design and synthesize a novel type of combined anti-tumor drug-doxorubicin modified silver nanoparticles(DOX-Ag NPs)with pH response,characterize its physical and chemical properties,and investigate its drug responsive release and anti-tumor activity in vitro.Methods DOX-Ag NPs were prepared by coupling silver nanoparticles (Ag NPs) with doxorubicin (DOX) via a LA-NHNH2linker. The structure of LA-NHN=DOX was confirmed by nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS).The particle size and micromorphology of the nanoparticles were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The optical properties of the nanoparticles were characterized by UV-vis absorption spectroscopy and fluorescence spectroscopy.The DOX release kinetics of DOX-Ag NPs under different pH conditions were examined by dialysis method combined with fluorescence spectroscopy. The in vitro anti-tumor effects of DOX-Ag NPs were evaluated by MTT assay. Results DOX-Ag NPs were spherical nanoparticles with a particle size of (40.4 ± 3.8) nm. DOX-Ag NPs could rapidly release DOX under weak acid condition.DOX-Ag NPs significantly inhibited the proliferation and cell viability of HepG2 cells in concentration dependent manner.When DOX concentration was 0.5-20 mg/L(Ag concentration was 0.45-18 mg/L), the cell survival rate was significantly lower in DOX-Ag NPs group than that of DOX group and Ag NPs group(P<0.05). Conclusion DOX-Ag NPs are a combined anti-tumor nano-drug with pH-responsive ability, which can release DOX rapidly in tumor tissues and play an anti-tumor effect through synergistic treatment with Ag NPs in vitro.