Preparation Of Black Phosphorus-based Nanocomposites And Their Application In Tumor Therapy

Cancer has become the second most serious disease in the world after heart disease.Human beings have spent a huge amount of manpower and financial resources to treat cancer,but the situation of cancer is still very serious.Among many methods for cancer treatment,radiotherapy,light therapy and combined chemotherapy based on nanomaterials are expected to solve the problems of low targeting and toxic side effects of single chemotherapies,which have become a research hotspot in the field of cancer therapy.Compared with traditional nanomaterials,two-dimensional nanomaterials(such as graphene,etc.)are more widely used in biomedical fields due to their large specific surface area,good photoelectric catalytic activity and biocompatibility.While black phosphorus(BP)is an emerging two-dimensional material discovered in recent years.It has extremely low cytotoxicity,excellent biodegradability,photodynamic and photothermal therapeutic ability,and higher specific surface area than graphene.As a result,it has gradually become the first choice of two-dimensional material for tumor treatment.However,there are still some defects in the practical application of BP,and its biological characteristics need to be further explored.Therefore,based on the strong application prospect of BP in the field of cancer therapy,two kinds of BP nanocomposites were designed in this paper to solve and optimize the application of BP in cancer therapy,and to further evaluate and expand its anticancer ability.The main research contents are as follows:(1)BP was combined with Fe₃O₄@MnO₂ NaYF₄:Yb/Er/Nd upconversion nanoparticles(MUCNPs)and photosensitizer Ce6(MUCNPs@BPNs-Ce6)to coordinate the therapeutic light wavelength of BP,enhance the imaging function of BP and improve the hypoxic microenvironment of in-situ tumor.BP nanosheets were prepared by liquid phase stripping and MUCNPs were synthesized by hydrothermal method.Finally,the nano-therapeutic agents were prepared by amide bonding.Upconversion analysis showed that MUCNPs could convert 808 nm laser to 645-685nm region.According to the photothermal test,the temperature of MUCNPs@BPNs-Ce6 solution increased by 30?after 5 min irradiation.Cell and animal experiments have shown that the therapeutic agents prepared can aggregate at the tumor site via the high permeability long retention effect(EPR)and kill cancer cells in combination with magnetic resonance/fluorescence imaging guidance.(2)BP-loaded nanometer copper was mixed with chitosan gel(CS@CuNPs@BPNs)to obtain a new dressing that can be used for hemostasis,antimicrobial and recurrence prevention after tumor surgery.The BP nanosheets were also prepared by liquid-phase stripping,and then the copper nanoparticles were reduced in situ on the surface.Finally,chitosan and its derivatives were added to prepare the hemostatic thermo-sensitive gel.In vitro and in vivo experiments showed that the prepared composite gel had good hemostasis and degradation ability.The coagulation index was as low as 25.3%,and most of the gel could be degraded within two weeks.At the same time,BP improves the dispersion of nano copper,thus enhancing its Fenton-like catalytic activity,and generates a large amount of reactive oxygen species(ROS)for antibacterial and anticancer.Finally,antibacterial/anti-tumor synergistic effect can be realized at the wound site to prevent wound infection and tumor recurrence.