Construction And Efficacy Study Of Drug Delivery System For Photodynamic Therapy And Alleviation Tumor Hypoxia

Cancer is still a major human health problem due to its rapidly increasing morbidity and mortality.The common clinical tumor treatment methods include surgical resection,chemotherapy and radiotherapy.In addition,a lot of research has been devoted to finding safe and effective new treatments,which has opened up new ideas for the treatment of cancer.Fortunately,because of the unique physical and chemical properties of nanomaterials and the development of nanotechnology,combination therapy based on multiple functional materials within a single system is possible now.However,the environment of solid tumor is complex and abnormal,which is a big challenge for drug delivery and therapeutic effect.Due to the clearance of blood circulation and tumor heterogeneity,the accumulation of nanoparticles at the tumor site is not considerable only by passive targeting of enhanced permeability and retention(EPR)effect.The tumor anoxic environment makes it impossible for the nanoparticles to achieve long-term or even obvious therapeutic effect.This study attempted to realize efficient photodynamic therapy(PDT)without the restriction of anoxic environment.And based on the known problems,two kinds of anti-tumor nanoparticles were designed and prepared,and their anti-tumor effect have been evaluated.The main content has the following aspects:(1)Perfluorohexane loaded silver nanocages coated with chitosan/indocyanine greenThe silver nanobox was etched by nitric acid to obtain the silver nanocage with pore structure.After the ultrasonic loading of oxygen-carrying perfluorohexane(PFH),the composite of indocine green(ICG)and chitosan was coated to obtain PFH@Ag@Ch-I nanoparticles.Due to the photothermal conversion effect of the silver nanocage,PFH@Ag@Ch-I will heat up under the near-infrared light,which make the PFH with low boiling point vaporize to release oxygen and promote the photodynamic therapy(PDT)of ICG in anoxic environment.So that a large number of cytotoxic reactive oxygen species was generated.On the other hand,the expanded PFH caused the nanoparticles to be exploded to achieve the effect of lysosome escape.Meanwhile,the reaction of exploding silver nanocage and hydrogen peroxide in the tumor further increased the level of reactive oxygen species.In vitro and in vivo experiments have demonstrated the high ROS generation level and anti-tumor performance of PFH@Ag@Ch-I in anoxic environment.(2)ZnO-gold nanoparticles/CPPO composite membrane liposomesZinc oxide is an inorganic photosensitizer that does not require oxygen to participate in the generation of reactive oxygen species by type I PDT.A composite membrane liposome ZnO-Au/CPPO Lips-CM with ZnO-Au nanoparticles in aqueous phase,bis(2,4,5-trichloro-6-carbopentoxyphenyl)oxalate(CPPO)in lipid phase and phospholipid layer doped with cancer cell membrane was designed.The energy generated by the reaction of CPPO and hydrogen peroxide in the tumor can stimulate ZnO to generate reactive oxygen species by type I PDT,while gold nanoparticles can compete with tumor cells to decompose nutrient glucose and produce hydrogen peroxide to support the continuation of the previous reaction.Cellular uptake experiments have shown that,due to homologous targeting,the tumor cell membrane composite on surface can have been more ingested and accumulated in homologous cells.In animal experiments,ZnO-Au/CPPO Lips-CM also effectively inhibited tumor growth and achieved clearance effect.