Self-assembled Nanomaterials Based On Graphite Phase Carbon Nitride Quantum Dots And Camptothecin For Synergistic Treatment Of Tumors

Graphite-like carbon nitride,as a new two-dimensional metal-free polymer material,has a suitable band gap in the visible light range,and has good biocompatibility,low toxicity,high fluorescence quantum yield and excellent physical and chemical stability.Therefore,it has shown good application prospects in the fields of photocatalysis,electrocatalysis and optoelectronics.With its unique optical and electronic properties,graphite-phase carbon nitride has shown great prospects for biomedical applications in bioimaging,detection of biomolecules,sensing,antibacterial and anti-inflammatory,and photodynamic therapy.As a new type of non-invasive therapy,sonodynamic therapy uses ultrasound to activate sensitizer compounds accumulated in tumors to generate reactive oxygen species,such as singlet oxygen,superoxide anions,and hydroxyl radicals,thereby causing irreversible damage to tumor tissues.And compared to photodynamic therapy,ultrasound has a strong tissue penetrating ability.Focused ultrasound can focus sound energy on deep tissues non-invasively,so sonodynamic therapy is very suitable for tumor treatment in deep tissues.In this study,a top-down method was used to prepare carbon nitride quantum dots.Due to their ultra-small size,carbon nitride quantum dots have good sonodynamic therapeutic potential.Carbon nitride quantum dots,Mn²⁺,and the natural drug camptothecin are self-assembled under the action of the amphiphilic polymer PLGA-PEG to obtain a theranostic nanoplatform integrating bioimaging and sonodynamic/chemotherapy.The full text is divided into four chapters.In the first chapter,we review the structural properties and synthesis methods of carbon nitride quantum dots and their applications in biomedicine,introduce the sonodynamic therapy,chemotherapy and self-assembly mechanism,and finally proposes the research ideas of this article.In Chapter 2,we first prepared bulk carbon nitride by calcination,and then prepared ultra-small carbon nitride quantum dots（CNQDs）using high-temperature oxidative pyrolysis assisted ultrasonic peeling.The mean particle size of CNQDs is about 5 nm,it is in a uniform monodispersed state and can exist stably in aqueous solution.Furthermore,through the hydrophilic and hydrophobic interactions between the components,the CNCP nanocomposite was prepared by self-assembly of CNQDs with Mn²⁺,the chemotherapeutic drug camptothecin,and the amphiphilic polymer PLGA-PEG.The CNCP nanocomposite was characterized by fluorescence spectroscopy,ultraviolet-visible absorption spectroscopy,infrared spectroscopy and TEM.And we further studied the sonodynamic effect of carbon nitride quantum dots,the loading of camptothecin,the MRI performance of the nanocomposite,thesonodynamic property of the final material,and explored the types of active oxygen.The influence of the different proportions of each component on the morphology of the final material and the optimal amount of feed are discussed.Due to the doping of manganese,CNCP shows obvious MRI contrast agent effects on a 0.5T MRI machine.In the sonodynamic effect verification experiment,it was found that CNQDs have good sonodynamic effects,and it is expected to play a synergistic effect with camptothecin to achieve synergistic treatment of sonodynamic and chemotherapy.In the third chapter,we further explore the application of the prepared material CNCP at the cell and living levels.The MTT experiment of 4T1,He La and HUVEC cells showed that CNCP has lower cytotoxicity,and the hemolysis experiment showed that CNCP has good blood compatibility.CNCP has a good MRI effect at the cell and living body level.Under ultrasound irradiation,CNCP showed obvious killing effect on 4T1 cells and He La cells,and the calculation of the synergy coefficient further proved that CNQDs and camptothecin can achieve synergistic treatment of sonodynamic and chemotherapy.In vitro and in vivo treatment experiments show that CNCP can effectively trigger the generation of reactive oxygen species under ultrasound irradiation,thereby realizing the synergistic effect of sonodynamic therapy and chemotherapy to kill cancer cells and inhibit tumor growth.In the fourth chapter,we comprehensively analyze and summarize the results obtained from the preparation,characterization and application of related materials in tumor diagnosis and treatment,and finally make a further prospect of the future application of the material in biomedicine.