| As a new layered semiconductor material,black phosphorus(BP)is a widely used photosensitizer due to its excellent optical properties and good biocompatibility.BP can generate singlet oxygen with obvious cytotoxicity under laser irradiation,which indicates potential applications in photodynamic therapy(PDT).However,the PDT efficiency of single BP nanosheets is severely restricted by the special microenvironment of tumor cells,such as low oxygen concentration for singlet oxygen generation and high singlet oxygen consuming by large glutathione concentration.BP with special drape structure has large specific surface area and can be applied as a carrier to effectively load organic molecules,functional nanoparticles and other substances.Therefore,it is reasonable to improve PDT efficiency by designing BP nanocomposites.In this paper,we focus on the development of BP-based nanocomposites to improve PDT efficiency by loading magnetic nanoparticles and functional organic molecules.We prepared a variety of nanocomposites that can achieve high PDT efficiency due to their excellent optical properties.We also further verified the biosafety and therapeutic effect of nanocomposites at the cellular level.The main innovative achievements of this thesis are as follows.(1)Preparation and properties of highly stable aqueous phase black phosphorus quantum dots(BPQDs).PEG@BPQDs with high stability and good fluorescence efficiency were prepared directly in aqueous phase through ultrasonicassisted liquid phase exfoliation and solvothermal method,in which NH2-PEG-NH2 was used as a surface passivation and modification agent.The aqueous PEG@BPQDs show an absolute quantum yield of 11.5%.In addition,the 6-month follow-up monitoring experiment showed that BPQDs dispersed in water show little degradation or fluorescence attenuation.Therefore,BPQDs has good fluorescence stability.Cell experiments show that PEG@BPQDs are a kind of potential fluorescence imaging material with good biocompatibility and cell fluorescence imaging performance.(2)Preparation and properties of BP-MnFe2O4@glucose oxidase(Gox)nanocomposites.Firstly,the solvothermal and phase transfer methods are proposed to prepare water-soluble ultrasmall superparamagnetic MnFe2O4 nanoparticles.Then,MnFe2O4 and Gox were linked by esterification to prepare MnFe2O4@Gox,which was loaded on the photosensitive BP nanosheets by electrostatic interaction to obtain BP-MnFe2O4@Gox nanocomposites.The experimental results indicate that MnFe2O4 has good superparamagnetism and the saturation magnetization of MnFe2O4 is significantly increased by 21%due to the change of surface modification molecules during phase transfer.Magnetic resonance imaging analysis shows that MnFe2O4 exhibited good magnetic resonance imaging performance(r2=165.3mM-1s-1).Moreover,BP-MnFe2O4@Gox nanocomposites are also a kind of good T2 contrast agent with the r2 value of 18.12 mM-1s-1.Moreover,MnFe2O4 in the nanocomposites exhibits catalase-like function and can synergize with Gox to realize a cyclic H2O2 catalytic decomposition,thereby significantly increasing oxygen concentration for sufficient oxygen for PDT and continuously depleting glucose to achieve starvation treatment.The cell experimental results show that the nanocomposites have good biocompatibility.Under laser irradiation of 660 nm,BP-MnFe2O4@Gox nanocomposites have good singlet oxygen generation ability and can effectively kill tumor cells in both normoxic and hypoxic environments.Therefore,the nanocomposites have both PDT and starvation therapy functions,showing good tumor cell killing effect.BPMnFe2O4@Gox is a kind of multifunctional nanocomposites integrating therapy and bioimaging.(3)Preparation and properties of BP-Au@MnO2-Chlorin e6(Ce6)nanocomposites.Firstly,Au@MnO2 nanoparticles were prepared by liquid reduction method and seed medium method.Subsequently,Au@MnO2 nanoparticles and the photosensitizer Ce6 were loaded on the surface of BP nanosheets modified by PEI through electrostatic interaction.The experimental results show that under laser irradiation of 660 nm,the photosensitivity of BP and the plasmon resonance effect of Au nanoparticles endow the nanocomposites good singlet oxygen generation ability.And loading of Ce6 can further increase singlet oxygen generation efficiency of nanocomposites.At the same time,MnO2 can not only reduce H2O2 to O2,which provides the adequate source for singlet oxygen generation,but also consume highly reductive glutathione to reduce the singlet oxygen consumption.The cell experiments show that the nanocomposites have good biocompatibility and can generate a large amount of singlet oxygen under laser irradiation,which can effectively kill tumor cells in normoxic and hypoxic environments to achieve high PDT efficacy.Therefore,BP-Au@MnO2-Ce6 is a kind of good nanocomposites for PDT. |
