Nanomaterials Based On Brush Polyphosphate For Photodynamic Therapy For Pancreatic Cancer

Objective photodynamic therapy has attracted wide attention from relevant clinical researchers.But due to the tumor specificity of tissue,tumor cells different from normal cell morphology,physiological characteristics,the photodynamic therapy is facing a great challenge in the diagnosis and treatment of tumors,and the nano material brush Polyphosphoester preparation in recent years has been widely used in clinical treatment of various cancers based on,also achieved a certain effect,so how effectively such nano materials and photodynamic therapy combined and study its effect in the treatment of cancer,is a hot topic of current research,so in this paper we design a kind of photodynamic therapy by nanoparticles brush Polyphosphoester materials preparation,and encapsulation for Ce6 and explore the photosensitizer for the treatment of pancreatic cancer,and achieved certain results,which will provide for the clinical application of photodynamic therapy in the treatment of cancer The new theoretical basis.Methods We use a brush with different PEG density Polyphosphoester nanoparticles P(CEP₃₀-EEP₁₀)/Ce6,P(CEP₂₅-EEP₁₅-PPEG₅)/Ce6 or P(CEP₃₀-EEP₁₅-PPEG₁₀)/Ce6 can be formed after the encapsulation of photosensitizer Ce6 drug loaded nano stable system,using NMR,particle size and electron microscope and HPLC method to check the structure,shape and size were characterized,and the detection of intracellular drug release.First of all,on the cell level,we used flow cytometry（FACS）,laser scanning confocal microscopy（CLSM）and high performance liquid chromatography（HPLC）to detect the difference of cell uptake of different nanoparticles under the same conditions.The reactive oxygen indicator（DCFH-DA）was used to observe the production of reactive oxygen species（ROS）after the uptake of different nanoparticles.MTT method was used to detect the killing effect of photodynamic therapy on cells.In the animal level,first,using small animal imaging were detected by enrichment of nano drug nanoparticles change with time in ICR mice blood circulation,metabolism and tumor bearing mice at different time points;then take the intravenous injection of different nano drug on tumor bearing mice after the same conditions under the light treatment,body weight and tumor volume were recorded periodically changes,and finally remove the mouse main organ and tumor apoptosis and proliferation of tumor cells and detection of tissue staining,to investigate the growth inhibition of tumor bearing mice with different PEG density nanometers.Results We have successfully prepared compact spherical nanoparticles with a particle size of about 100 nm P(CEP₃₀-EEP₁₀)/Ce6、P(CEP₂₅-EEP₁₅-PPEG₅)/Ce6 and P(CEP₃₀-EEP₁₅-PPEG₁₀)/Ce6.At the cell level,it can be clearly seen that the P(CEP₃₀-EEP₁₀)/Ce6 without PEG chain is most consumed by cells,followed by P(CEP₂₅-EEP₁₅-PPEG₅)/Ce6andP(CEP₃₀-EEP₁P(CEP₃₀-EEP₁₀)/Ce6₅-PPEG₁₀)/Ce6uptake is relatively minimal,which is mainly due to the fact that PEG has reduced cell uptake rate.Due to the difference of their uptake,there is also the same difference in the production of reactive oxygen species after the late illumination.The more intake,the more oxygen production is produced after illumination,and the stronger the killing effect on cells.At the animal level,because the PEG modification can increase the hydrophilic drug,so that it is not easy to be plasma protein adsorption,and not easy to be eliminated the phagocytic cells,polyphosphoester nano materials can exist stably in theintestinaltractinlongcycle,andthecelluptakedifference,P(CEP₂₅-EEP₁₅-PPEG₅)/Ce6 at tumor site the amount is maximum,followed by P(CEP₃₀-EEP₁₅-PPEG₁₀)/Ce6,P(CEP₃₀-EEP₁₀)/Ce6 is the worst,because it is very easy to be blood in vivo at tumor site rapid clearance,the reduced amount of.EPR effect finally arrived at the tumor site by nano drug tumor in enrichment of the site of the tumor,realize its uptake by tumor cells,the release of large amounts of photosensitizer,light to produce reactive oxygen strong killing effect,complete the antitumor effects of photodynamic therapy.Conclusion The different PEG density of polyphosphoester nano drugs have significantly different effects on tumor inhibition,the PEG density is too big or too small,the effect is not good,moderate density P(CEP₂₅-EEP₁₅-PPEG₅)/Ce6 inhibitory effect is the best,this is because it can not only exist in the blood circulation to achieve stable long,and it is good to be tumor cell uptake,the accumulation of photosensitizer Ce6 in tumor site,producing more ROS makes the subsequent photodynamic therapy,and thus produce better killing effect on tumor cells,inhibit the growth of the tumors.The study provides a new theoretical basis for further research on the combination of polyphosphate materials and photodynamic therapy for the treatment of various cancers.