Study On The Preparation And Application Of Polypyrrole Based Nanotheranostic Agents

Integrating diagnosis and therapy is the key target of the domain for cancer research.Above all,the building of multifunctional nanotheranostic agent stands out.Recently,photothermal therapy(PTT)draws increasing attention as its advantages of less invasiveness and higher specificity.To ensure a more effective treatment,it is important to combine the imaging technique and therapy together.Magnetic resonance imaging(MRI)is one of the noninvasive and reliable imaging technologies,which could provide physiological information with high specific and temporal resolution of soft tissue imaging,especially suitable for cancer diagnosis.Moreover,through introducing contrast agents,the sensitivity of MRI can be greatly improved.Polypyrrole(PPy)is a kind of conjugated polymer,attribute to its good biocompatibility,high absorption efficient during NIR region,and excellent photo stability,the outstanding PPy holds great potential for fabricating PTT agent.However,PPy has stable chemical structure and cannot be functionalized readily.In order to remove this obstacles,in this thesis polydopamine(PDA)and bull serum albumin(BSA)were selected to modify the PPy,which can be further connected by MR contrast agents to construct nanotheranostic agent for cancer diagnosis and therapy.In the second chapter,PPDE with uniform core-shell structure was build successfully.The obtained nanoparticles have uniform shape with the average size of 150 nm and can disperse well in watery environment.PPDE possess obvious absorption during near infrared ray(NIR)region,under the NIR laser(808 nm,1.5 W cm-2),temperature elevation can be detected in the PPDE dispersions,verified the good photothermal properties of PPDE.Moreover,the PDA shell contains plentiful phenolic hydroxyl groups which can chelate with iron ion to serve as T1-modal MR contrast agent,and the relevant ongitudinal relaxivity(r1)was calculated to be 5.05 mM-1 s-1 by the clinical MRI scanner,and PDA also provides the activate sits for further conjunction of PEG chain to ensure the long circulation time in vivo.Excellent biocompability of PPDE was confirmed by relevant MTT assay,corresponding in vitro and in vivo experimental results suggested that then obtained PPDE can be employed for T1-weighted MRI guided PTT.In the third chapter,PPy@BSA-Gd nanocomposite was fabricated through "one pot" method,using the natural BSA as the stabilizer for Pyrrole polymerization and the biomimetic mineralization of gadolinium oxide.The average size of obtained nanoparticles was 50nm,and it has excellent stability in aquatic conditions.Verified by the photothermal therapy assay,PPy@BSA-Gd could absorb 808 nm NIR laser and converted it to sufficient heat to kill the cancer cells.According to the results of MTT and cellular fluorescence tests,PPy@BSA-Gd had good biocompability and can be taken up by the cancer cells.During the MRI test,the tumor section of mice getting bright with time after tail veil injection of PPy@BS A-Gd,confirmed that the obtained nanoparticle have long blood circulation time to ensure its accumulation in the tumor site through EPR effects and can serve as the T1-wrighted MR contrast agent.In the in vivo PTT assay,the tumor of treated group showed dramatic regression without regeneration with the observing period for 14 days.All the corresponding results verified that PPy@BSA-Gd possess great potential for cancer diagnosis and therapy.