Synthesis And Theranostic Application Of Activatable Ultrasmall Gold Nanorods

Purpose:We obtained the multi-functional nanoprobes activatable ultrasmall gold nanorods(AUGNRs)that combined photothermal therapy and activatable fluorescence imaging.Characterization and function were measured,and the effect of fluorescence imaging and photothermal therapy for breast tumor cells was evaluated Method:The UGNRs were synthesized by one-pot seedless technique.Then,the UGNRs were surface modified with mercaptoethylamine and combined with fluorescein Cy5.In this way,activatable ultrasmall gold nanorods(AUGNRs)that realize ‘‘off–on'' switched fluorescence imaging-guided efficient PTT were obtained.Besides,different kinds of characterization were measured,including transmission electron microscopy(TEM),UV-vis-NIR spectrophotometer,dynamic light scattering(DLS)and zeta potential.The biocompatibility,effect of fluorescence imaging and photothermal of the probe were then evaluated by using breast cancer 4T1 cells.The bold-half time and biodistribution in vivo was measured by 4T1 tumor mice.Results:(1)TEM showed that the obtained AUGNRs had a long diameter × minor diameter was about(18 nm × 4 nm),the dispersibility was excellent and particle size was uniform.The UV-Vis-NIR curves shown in the UV spectrophotometer have two distinct absorption peaks at 525 nm and 805 nm,respectively.The hydrated particle size is about 21.7 ± 2.7 nm and the surface potential is 10.12 ± 1.15 mV.(2)The temperature of AUGNRs aqueous solution increased obviously at exposure of 808 nm near infrared light,but the temperature of pure water was not obvious,which indicated that it has a good photothermal effect,can be mediated to realize photothermal therapy.(3)AUGNRs were mixed with the concentration of GSH in tumor cells,the fluorescence signal was significantly increased,the fluorescence effect was obvious.Indicating that AUGNRs had an excellent fluorescence specificity,sensitivity and reactivity.(4)AUGNRs were incubated with breast cancer cells 4T1 for 24 h,and the cell viability did not decrease significantly compared with the control group.The good biocompatibility showed that it could be used in vitro and in vivo.Under the exposure of near infrared light irradiation,4T1 cells were killed obviously,which indicated that AUGNRs had a great effect of photothermal therapy.(5)In the cell fluorescence imaging experiment,there was a significant Cy5 fluorescence signal in 4T1 breast cancer cells under fluorescence microscope,but no Cy5 fluorescence signal was observed in 293 T cells.These results indicated that AUGNRs could be effectively taken up by tumor cells and could induce fluorescence signal induced by high concentration of GSH in tumor cells,but could not activate the fluorescence signal of AUGNRs in normal cells.(6)The blood half-time of AUGNRs in vivo was about 4.574 h.(7)AUGNRs were mainly distributed in the kidney 1 day after injection into the body,and the tumor was also enriched.On the 7th day after injection,the contents of each organ were significantly decreased,but the tumor was higher,which indicated that AUGNRs can be efficiently enriched in the tumor site.Conclusion:The AUGNRs prepared in this study have good dispersibility,uniform particle size,excellent biocompatibility,great photothermal properties and fluorescence reactivity.It is of great significance for the clinical transformation of visualization of cancer with precise photothermal therapy.