Research On Multifunctional Nanocomposites For Tumor Visualized And Combined Therapy

With the growing threat to human life and health from malignant tumors,researchers have been exploring various effective diagnostic and therapeutic methods over the years.In this study,we designed and constructed a multifunctional therapeutic system based on indocyanine green(ICG)-loaded PEGylation silver nanoparticle core/polyaniline shell(Ag@PANI)nanocomposites(ICG-Ag@PANI)for multi-modal imaging-guided tumor visualized and combined therapy.In this study,many properties of the nanocomposite were characterized and evaluated.We also assessed the therapeutic effect in vitro and in vivo.It was proved that the biodistribution and intratumoral accumulation of the nanocomposite could be real-time monitored by multi-modal imaging,guiding the tumor visualized and combined therapy.In this study,ICG-Ag@PANI was fabricated by loading the ICG molecules with aromatic structures onto the conjugated polymer PANI shell layer with delocalized π-electrons.The average particle size of ICG-Ag@PANI was 121.6 nm with homogeneous dispersion.ICG-Ag@PANI had strong absorption in the near infrared(NIR)region,and the maximum absorption peak was about 810 nm.The loading capacity of ICG could reach a maximum about 50%.The results proved that loading ICG onto Ag@PANI nanovehicles endowed ICG with outstanding photostability and storage stability.ICG-Ag@PANI exhibited excellent photothermal effect and singlet oxygen generation.In this study,HeLa cells were used to investigate the in vitro effect of the nanocomposite.The results showed that the cellular internalization level of ICG could be heightened after loading onto Ag@PANI nanovehicles.The endolysosomal escape behavior could be triggered by NIR laser.Intracellular reactive oxygen species(ROS)test showed that ICG-Ag@PANI could play an effective photodynamic therapy(PDT)effect at the cellular level.The effect of killing tumor cells could be evaluated intuitively by Calcein-AM/PI double staining.Flow cytometry analysis showed that the cell apoptosis and necrosis rate reached up to 74.1% after treating with ICG-Ag@PANI plus laser irradiation.MTT results showed that ICG-Ag@PANI could generate strong phototoxicity to cells.In this study,the mice tumor models were established to examine the anti-tumor effect of ICG-Ag@PANI in vivo.Near-infrared fluorescence(NIRF)imaging showed that ICG-Ag@PANI could accumulate in the tumor by enhanced permeability and retention(EPR)effect and reach the maximum amount after 24 h injection.Because of the highly sensitive photoacoustic property of ICG-Ag@PANI,the biodistribution in tumor area could be observed by photoacoustic imaging(PA)technology.Near-infrared thermal images showed the effective in vivo photothermal effect of ICG-Ag@PANI,while the in vivo ROS test confirmed the excellent PDT effect.ICG-Ag@PANI could play the best PTT/PDT synergistic effect after laser irradiation with good biosecurity and no long-term toxicity.In summary,the ICG-Ag@PANI multifunctional nanocomposite could realize the visualized PTT/PDT combination therapy that was driven by 808 nm single light and synchronously guided by NIRF/PA/thermal tri-modal imaging.ICG-Ag@PANI had a great prospect in multi-modal imaging-guided tumor visualized and combined therapy.