AIE-functionalized Glycogen For CpG ODN Delivery And Tumor Treatment

Cancer continues to threaten human life and health,and how to cure cancer is currently a hot research topic.Immunotherapy utilizes the human immune system to treat cancer.It activates immune cells to recognize the tumor antigens,induces immune cells to clear tumor cells,and thus achieves the goal of curing cancer.Cp G ODN can simulate the bacterial and viral DNA to stimulate the mammalian immune system and induce natural and acquired immune responses.However,free Cp G ODN has a low cellular uptake rate and is easily degraded by nucleases in vivo.Glycogen is a macromolecular polymer connected by glucose molecules.It has a natural spherical dendritic nanostructure and has good biocompatibility and degradability.It is an ideal nano-drug delivery carrier.Our previous studies showed that glycogen could specifically deliver Cp G ODN into the lysosome of immune cells and effectively release it,thereby significantly improving the immune stimulation.Based on the above analysis,the aminoglycogen carrier was prepared,and the AIE-type photosensitizers TTVBA and Cp G ODN were further loaded by electrostatic adsorption,and a multifunctional nano-drug delivery system was constructed for the immune-photodynamic synergistic therapy of tumors.The main research content of this paper is as follows:(1)Construction and characterization of multifunctional nanocarriers(TG).In this thesis,we synthesized positively-charged amino glycogen(NG).The zeta potential and particle size of NG were +38 m V and 65.8 nm,respectively.NG entraps AIE-type photosensitizers(TTVBA)via electrostatic forces and abundant cavities,constructed a multifunctional nanocarrier TG.TG has certain photobleaching resistance and reactive oxygen generation ability.At the same time,TG has good safety and blood compatibility,and can be used as a fluorescent probe to realize intracellular imaging.(2)Preparation and characterization of TGC NPs and their photodynamic anti-tumor effects in vitro.Cp G ODN was loaded on TG through electrostatic interaction to construct nanodelivery system TGC NPs.TG can efficiently load Cp G ODN,and TGC NPs could protect Cp G ODN against nuclease degradation and improve the cell uptake rate of Cp G ODN.The particle size and zeta potential of TGC NPs were 140 nm and +23.8 m V,respectively.TGC NPs produce a large amount of cytotoxic ROS under light conditions,which can effectively kill tumor cells and inhibit the migration of tumor cells.(3)TGC NPs tumor immune-photodynamic synergistic therapy in vivo and in vitroTranswell experiments were used to explore the therapeutic effect of TGC NPs on tumor in vitro immune-photodynamic synergistic anti-tumor,and it was found that TGC NPs treated with light can effectively induce macrophage migration and have a good anti-tumor effect.TGC NPs can induce the expression of co-stimulatory factors CD40 and CD80 on the surface of macrophages and the secretion of anti-tumor cytokines IFN-γ,TNF-α and IL-6,indicating that TGC NPs can effectively induce macrophages to play the role of tumor immunotherapy in vitro.TGC NPs have no toxic side effects on the main tissues and organs of mice,and have good safety.TGC NPs were mainly enriched in tumor tissues,which was beneficial to play the role of photodynamic anti-tumor.At the same time,TGC NPs can also induce the secretion of anti-tumor cytokines in mice,which has the effect of tumor immunotherapy.Light-mediated TGC NPs can exert good immune-photodynamic synergistic antitumor effects both in vivo and in vitro.In summary,TGC NPs show good application prospects as nanodrug delivery system that combines Cp G ODN-mediated immunotherapy and PDT.