Glyco-Targeting Nanorods Construced By AuNRs@MSN Modified Via Host-guest Complex Of Pillar[5]arene For Cancer Multi-Mode Therapy

Cancer has become one of the major diseases threatening human health and even life.At present,the common therapy methods mainly include chemotherapy,photodynamic therapy,etc.,but their therapeutic efficiency is limited by the defects of the drug itself and the hypoxic tumor microenvironment.Emerging treatments,such as gas therapy(GT)and alkyl radical therapy(ART),offer a novel way to address these problems.With the development of nanotechnology,its potential in the field of drug delivery has been increasingly explored.Nano drug delivery systems based on inorganic materials provide a new opportunity for multi-mode synergetic treatment of cancer.For example,mesoporous silicon-coated gold nanorods(AuNRs@MSN)have unique advantage in the construction of multi-mode therapy nanocarriers based on photothermal responsiveness due to their good biocompatibility,photothermal conversion efficiency and other characteristics.Based on this,this paper designed and constructed a multi-functional AuNRs@MSN based nanorods,namely AuNRs@MSN-SNO@NP5G,to load the thermal-sensitive alkyl free radical(R·)releasing molecule(AIBI)to achieve multi-mode GT/ART/PTT therapy of tumor.The contents of the thesis include:(1)Preparation and characterization of A-AuNRs@MSN-SNO@NP5G:First,gold nanorods(AuNRs)with high monodispersity were synthesized by sodium oleate assisted method.Mesoporous silicon(MSN)was coated on the surface of AuNRs by improved St?ber method and sulfhydrated.Then thermal-sensitive nitric oxide(NO)releasing molecules,S-nitrosothiols(R-SNO),was modified on the surface of AuNRs@MSN via chemical methods,and AIBI was loaded into the mesoporous.Then,upon electrostatic interactions and host-guest interactions,the amino pillar[5]arene(NP5)and galactose derivative(G)were coated on the surface of A-AuNRs@MSN-SNO,and the final nanoparticles A-AuNRs@MSN-SNO@NP5G were obtained.Through ~1H NMR,Zeta potential,Griess reagent,Ellman reagent,UV-Vis,TEM,FT-IR,and other experimental methods,verified the gradual construction of the system and demonstrated good stability,dispersion,photothermal conversion properties,NO release,and R·production and influence factors.(2)Study on anticancer effect:Confocal laser scanning microscopy experiment and flow cytometry analysis demonstrated that the nanocarrier could be effectively uptake by Hep G2cells with specific targeting ability.In addition,upon 808 nm NIR irradiation,confocal laser scanning microscopy experiment showed that AuNRs generated hyperthermia due to its photothermal conversion property,which induced cytotoxicity of multi-mode therapy.Furthermore,MTT assay verified that the nanocarrier had good biocompatibility with no obvious toxic and side effects on normal cells,but showed a good killing effect on cancer cells.In this thesis,a glyco-targeting nanorods construced by AuNRs@MSN modified via host-guest complex of pillar[5]arene was constructed and successfully applied to cancer multi-mode therapy.it expands provides the application of supramolecular hybrid system in nanomedicine.This study not only enriched the supramolecular hybrid drug delivery system,expanded the application of supramolecular hybrid system in the field of nanomedicine,but also provided a new idea for the near infrared light(NIR)controlled OFF/ON multi-mode therapy.