Development And Applications Of Carbon Nanomaterials-Based Drug Delivery Systems And Theranostics

Small molecular drugs play important role in agriculture and biomedical fields.However,the inherent shortcomings of free drugs such as poor aqueous solubility and physiological stability have significantly hindered their efficacy in practical application.Recently,nanomaterials have been widely used as drug delivery carriers to increase the drug bioavailability.Among various nanomaterials,carbonaceous nanomaterials,e.g.graphene oxide(GO),carbon nanoparticles(CNPs),possess great promise in this aspect for their ultrahigh drug loading capacity,well stability,good biocompatibility,and low environmental risk.Therefore,in this thesis,the author demonstrates the use of GO and CNPs as efficient nanocarriers for anticancer drugs and pesticide.(1)In the first section of the second chapter,the author used single-layer GO as the carrier for loading and delivery of methylene blue(MB),a small molecular dye in printing and dyeing industry,and a drug in medicine,and studied the loading rule of MB loaded on GO.Through the analysis of adsorption kinetics,adsorption isotherm,and adsorption thermodynamics,information such as the maximum drug loading capacity of GO,the equilibrium time of the adsorption process,and the optimal drug loading strategy,were collected.The above information could provide guidance for optimal drug delivery application in practice.Therefore,based on the positive result in the first section,the author further studied the drug loading performance of GO for avermectins(AV),a widely used biopesticide,and promoted the application of GO in agriculture field.GO exhibited ultrahigh loading capacity for AV,with the maximum loading capacity of 1428 mg/g.By loading on GO,the water solubility of AV was significantly improved.Besides,owing to the protection of GO,the anti-photolysis performance of AV improved substantially.Compared with free AV,AV loaded on GO exhibited significantly enhanced anti-insect effect.(2)Like GO,carbon nanoparticles(CNPs)possess excellent drug loading performance,good photostability and biocompatibility,which make them ideal drug carriers.Indocyanine green(ICG)is a near infrared fluorescence(NIRFL)imaging agent,but its photostability is poor,and it also suffers from its weak tissue penetration and poor resolution.Therefore,in the third chapter,the author designed magnetic iron oxide modified CNPs(MCNPs)as the carriers for ICG.Owing to the protection of MCNPs,ICG exhibited dramatically improved photostability.Besides,the magnetic resonance(MR)imaging performance can remedy the defect of NIRFL imaging.The combination of the two imaging models could provide accurate information of the tumor area and size.This nanotheranostic platform has successfully overcome the defect of ICG,realizing prolonged in vivo circulation time and improved tumor targeting of ICG,and dual-modal imaging guided photothermal therapy(PTT)effect.(3)Chemotherapy is one of the most commonly used anticancer methods.However,the obvious side effect,nonspecific tumor targeting,and low drug utilization of anticancer drugs have greatly limited its application.To overcome these shortcomings and realize controlled drug delivery and release,and more effective treatment effect,in the fourth chapter,the author designed a multifunctional theranostic platform based on hydroxypropyl-beta-cyclodextrin and Fe3O4 co-modified CNPs(HFCNPs)for smart drug delivery and imaging guided chemotherapy and PTT.HFCNPs possess good drug loading performance,and pH/NIR dual-stimuli responsive drug release property.This nanoplatform can specifically deliver doxorubicin(DOX),an widely used anticancer drug in clinic,to tumor site through the enhanced permeability and retention(EPR)effect,and can promote the release of DOX in tumor acidic microenvironment under NIR laser irradiation.Moreover,by using MR/NIRFL imaging,more detailed and clear information regarding tumor location,size,and boundary are obtained.Therefore,the strategy developed in this work can achieve smart drug delivery and release,and imaging guided enhanced chemotherapy in combination with PTT,leading to safe and effective tumor therapy.In addition,the NIR light induced hyperthermia can realize PTT of tumor.The combination of PTT with chemotherapy can inhibit tumor more effectively.