Simulation Analysis And In Vitro Bionic Experimental System Design Of Active Targeting Of Nano-preparations

Since the development of society,cancer is still a major problem that plagues mankind.In 2018 alone,there were approximately 18.1 million new cases and 9.6million deaths worldwide.Cancer has now become the “number one killer” threatening human health.Drug chemotherapy is a commonly used clinical treatment method,but its therapeutic effect is not ideal.Obviously,highly effective anti-cancer drugs have become a major demand for people’s healthy life.In recent years,the rapid development of nanotechnology has brought new hope for tumor treatment.However,at present,its therapeutic effect is still not ideal,because the abnormal microenvironment of the tumor causes the nano-preparations to not effectively accumulate in the tumor tissue.Therefore,an in-depth understanding of the entire transport process of nanopreparations in the body is the main means to improve therapeutic efficacy.The active targeting of nano-preparations to tumor cells generally needs to go through four stages,which are the transport of nano-preparations in blood vessels,the transvascular transport of nano-preparations,the transport of nano-preparations in the tumor stroma,and the entry of nano-preparations into tumor cells.Among them,the transvascular transport process of nano-preparations plays an important role,but this transport process is rarely studied.The influence of the abnormal microenvironment of the tumor on the transvascular transport process of nano-preparations is also rarely reported.There is always a lack of clear understanding of the vascular transport process.Therefore,this subject decided to study the influence of the tumor’s abnormal microenvironment on the transvascular transport of nano-preparations and explore the advantageous conditions of nano-preparations in the process of transport.In the process of the research,simulation and in vitro biomimetic experiments were used to explore the influence of the tumor’s abnormal microenvironment on the transport of nanopreparations across blood vessels.The mechanical behavior of the nano-preparation in the tumor microenvironment is analyzed.The flow parameters of the nano-preparation under the action of abnormal factors in the microenvironment are obtained.It reveals the inherent law of interaction between the hydrodynamic behavior and delivery efficiency,as well as the advantageous conditions of the nano-preparation in the transvascular transport process.In the context of the combination of medicine and engineering,it provides new insights into the delivery process of nano-preparations from a mechanical perspective.The research results provide important theoretical basis and support for the development of platform-based active targeted nano-drug delivery technologies and materials.A tumor-abnormal blood vessel-interstitial model was established based on the abnormal physiological structure of the tumor.The model used computational fluid dynamics(CFD)to simulate the transvascular transport process of the nano-preparation to visualize the delivery process of the nano-preparation.In the research process,the process of tumor deterioration was simulated by regulating the changes of the vascular endothelial cell gap and interstitial fluid pressure.Then,the effects of the changes in vascular endothelial cell gap,interstitial fluid pressure and blood flow rate on the transvascular transport process of nano-preparations were respectively explored.The results show that the increase of the vascular endothelial cell gap within a certain range will promote the nano-preparation to cross the blood vessel wall and enter the tumor interstitium.With the continuous increase of interstitial fluid pressure,the transvascular transport efficiency of nano-preparations gradually decreases.A more serious situation is that when the interstitial fluid pressure continues to increase to the pressure of the blood vessel wall,the pressure gradient between the blood vessel wall and the interstitium will disappear.At this time,the nano-preparation can hardly cross the blood vessel wall to enter the interstitial area,which causes the enhanced permeability and retention(EPR)effect of the nano-preparation to disappear.Through further simulation analysis,it is found that the pressure gradient between the blood vessel wall and the interstitium plays a leading role.Then,this conclusion is simulated and verified by using blood flow velocity.The results show that the pressure gradient between blood vessel wall and interstitium plays a decisive role in the transvascular transport of nanopreparations.In addition,an exciting conclusion has been obtained that increasing the blood flow rate in a small range will promote the transvascular transport process of the nano-preparation and improve the transport efficiency of the nano-preparation.In the design of the in vitro bionic experimental system,the Transwell chamber is used as the main body.First,determine the cell culture time,cell suspension volume,cell suspension concentration and other key parameters that meet the experimental requirements,and analyze and design cell implantation and culture programs.Then,different vascular endothelial cell gap experiment group 1 and different interstitial fluid pressure experiment group 2 were constructed to simulate the deterioration of the tumor microenvironment in vivo in vitro.The effects of changes in vascular endothelial cell space and changes in interstitial fluid pressure on the transport of nano-preparations across blood vessels were respectively explored to verify the conclusions of simulation.The experimental results show that the vascular endothelial cell gap increases continuously within a certain range,which will promote the nano-preparation to cross the blood vessel wall and enter the interstitium.This result is consistent with the simulation result.As the interstitial fluid pressure continues to increase,the transvascular transport efficiency of the nano-preparation will continue to decrease.A more serious situation is that when the interstitial fluid pressure continues to increase to the pressure of the blood vessel wall,it is difficult for the nano-preparation to transport across the blood vessel.This result is also mutually confirmed by the simulation results.This topic takes the process of nano-preparation transvascular transport as the research object.In order to clearly understand the impact of tumor abnormal microenvironment on the transvascular transport of nano-preparation,explore the interaction mechanism among them,and analyze the mechanical behavior of nanopreparation in the microenvironment.Simulation and in vitro biomimetic experiments were carried out on the transvascular transport process of nano-preparations.The subject research has provided strong theoretical and data support for the further development of platform-based nano-preparations,and has carried out beneficial attempts for the research and application path exploration of integrated medicine and engineering for the treatment of tumors.