Preparation Of Tumor Microenvironment Responsive Nanocarriers And Preliminary Studies On Their Biomedical Performance

In anti-tumor therapy,tissue barrier not only directly affects drug distribution and accumulation,but also reduces drug delivery efficiency and bioavailability.The penetration of drug carriers in tumor tissue is the bottleneck that limits the efficiency of drug delivery.To overcome this barrier,tumor microenvironment-sensitive materials have been developed to enhance tumor penetration.Tumor tissues are characterized by acidic and hypoxic microenvironments,and it is still a challenge to effectively utilize these endogenous stimuli to design carriers that can facilitate tumor tissue penetration.To solve this problem,this thesis attempts to develop two different types of nanoparticulate delivery systems:1)size-switchable nanoparticles responding to the tumor acidic microenvironment,2)nanomotors sensitive to tumor hypoxic microenvironment.Specific contents are as follows:1)Polymeric nanoparticles(D₂₃PMP)sensitive to tumor acidic microenvironment were prepared for enhanced tumor penetration.A series of p H-sensitive nanoparticles were obtained by adjusting the graft number of tertiary amine molecules and PEG on fourth generation polyamides?PAMAM?.The resultant D₂₃PMP had a large size??98 nm?under neutral conditions,but would quickly disintegrate into small particles??8 nm?under acidic tumor microenvironment?p H 6.7?.Furthermore,D₂₃PMP could load doxorubicin?DOX?,and the maximum drug loading content could be 26.17%.The results show that the size of the nanoparticles could be changed rapidly at p H 6.7 and effectively penetrate into the multicellular spheroids under the condition of tumor acidity,which had potential applications in overcoming the tissue barriers.2)A tumor hypoxic and sensitive nanomotor system was constructed,which is expected to transform the particles from passive diffusion to active infiltration by releasing oxygen in H₂O₂ solution and promote particle movement.In this system,the effects of particle size,surface modification,paraffin/particle mass ratio and surfactant concentration on particle distribution on the surface of the colloidosomes were investigated.Then,Si O₂ nanoparticles embeded colloidosome was chosen to prepare manganese dioxide?Mn O₂?nanomotors with adjustable sizes from 100 to 700 nm.A variety of characterization methods were used to prove the asymmetric structure of the Mn O₂ nanometer motor,and the motion of the Mn O₂ nanomotor was further analyzed.It was found that the nanomotor could move effectively in 0.5%H₂O₂solution,and its diffusion coefficient was 2.25 times higher than that in ultra-pure water,confirming the effective motion of the nanomotor.However,further research in the biomedical field of Mn O₂ nanomotors needs to be carried out.