Design,Construction And Anti-tumor Research Of Novel Nano-photosensitizer

Tumor metastasis is a fatal feature of malignant tumors,the primary factor leading to high mortality in cancer patients,and a major challenge to clinical treatment of cancer,which is regarded as the frontier of cancer research.Among them,photodynamic therapy is a new method of treating tumors.Under specific light irradiation,photosensitizers can generate a large number of reactive oxygen species.However,since the singlet oxygen generated by the photosensitizer has a very short existence time,the action distance is very limited,and it can only destroy biomolecules in close range.Therefore,the distribution of tumor cells limited by the photosensitizer determines that it can only effectively kill and inhibit tumor cells in situ.In this paper,we discovered a new class of nanomaterials,namely nanoparticles displayed on the surface of palmitic acid,during our experimental exploration.When the nanoparticle interacts with tumor cells,it can not only be efficiently taken up by tumor cells and distributed in the cells,but also can actively track tumor extracellular vesicles,exhibiting dual tumor spatial distribution characteristics that cannot be achieved by traditional nanoparticles.We further designed and prepared photosensitive nanoparticles displayed on the surface of palmitic acid(nanoparticles covalently loaded photosensitizer chlorin Ce6).Utilizing the dual tumor spatial distribution function of the nano-photosensitizer(which can not only distribute inside tumor cells,but also actively track tumor extracellular vesicles),it can achieve photodynamic killing of primary tumors while destroying its tumor extracellular vesicles,thereby Blocking the intercellular/tissue communication mediated by extracellular vesicles ultimately effectively inhibits tumor metastasis and recurrence.The work done is divided into the following points:1.Prepare nanoparticles displayed on the surface of palmitic acid.By using PLGA as a model hydrophobic block,design and prepare a new type of amphiphilic block copolymer with PLGA as the hydrophobic core and palmitic acid motif random copolymerization sequence as the nano shell.2.Using fluorescent confocal microscopy to study the ability of nanoparticles displayed on the surface of palmitic acid to be efficiently and quickly taken up by tumor cells and rapidly transfer into extracellular vesicles,especially the use of confocal Z-stack mode to study the ability of nanoparticles displayed on the surface of fatty acids after 3D reconstruction Distribution of particles in tumor extracellular vesicles.3.At the two levels of cells and extracellular vesicles,the dual tumor spatial distribution process of nanoparticles displayed on the surface of palmitic acid and the internal relationship between various influencing factors were explored by confocal imaging technology and flow detection technology.4.In vitro photodynamic characterization of nano-photosensitizers displayed on the surface of palmitic acid:first construct the nano-photosensitizers displayed on the surface of palmitic acid,and then prove that it has the ability to kill tumor cells through experiments such as MTT,cell death,and apoptosis.Scratch,cell transfer,cell invasion and other experiments have verified that it can inhibit tumor cell metastasis and invasion.Finally,Western blot was used to explore the mechanism of the nano-photosensitizer displayed on the surface of palmitic acid to inhibit tumor metastasis.5.In vivo photodynamic characterization of nano-photosensitizers displayed on the surface of palmitic acid:a lung metastasis model was constructed by orthotopically injecting tumor cells into mice.Then,the anti-tumor efficacy of nano photosensitizers displayed on the surface of fatty acids to simultaneously inhibit tumor growth and metastasis recurrence was systematically evaluated by the tumor growth curve,body weight change,number of lung metastatic nodules,and survival curve of tumor-bearing mice.In summary,the nano-photosensitizer displayed on the surface of palmitic acid will provide a new method for synchronous inhibition of tumor growth and metastasis recurrence.