Preparation And Properties Of Novel Self-assembled Nano-MRI Contrast Agents Based On Porphyrin And Ferrocene

Since magnetic resonance imaging (MRI) has high resolution in soft tissues imaging and no radiation, it has become one of the most important medical imaging technique in clinical, and plays an important role in the diagnosis and localization of tumors and other diseases. However, the sensitivity of MRI without contrast agent (CA) is low, so it is necessary to use CA to improve its sensitivity and accuracy. The currently used small molecule agents have drawbacks including short residence time in the blood compartment, poor specificity, and low imaging efficiency. Macromolecular and nano contrast agents due to their advantages of higher relaxivity, longer circulation time and tumor target ability, have received great research interest with the multi-functional and tissue-specific contrast agent as the most hottest directions.This thesis first briefly introduced the basic concept of MRI and its CA, the history of development, as well as the MRI research progress and prospective directions of CA with the emphasis on dendrimers and nanoparticles MRI CAs applications. In the thesis, we designed a novel nanoparticle CA with exact molecular structure, long blood circulation time, high relaxation rate, tumor targeting and photodynamic therapy function and a novel redox-responsive nano micellar CA.In the second part, a porphyrin derivative was synthesized and modified it with an reactive MRI CA DTPA-Gd3+and hydrophilic PEG. It formed10nm nanopartices in water after its self-assembly. It was found that it showed a relaxivity (r1) of1.6times higher than that of DTPA-Gd3+, and had longer blood circulation time than DTPA-Gd3+, as well as tumor-targeting capability, and was no-toxic to normal cells.In vivo imaging experiment showed its could significantly enhanced the tumor imaging.Unfortunately, it did not demonstrated the photodynamic therapy function as expected.However, its fluorescence properties make the CA a potential magnet-optical dual functional nano CA for tumor detection.In the third part, a nano micelle with a size of34nm was prepared from self-assembly of a amphiphilic block polymer that was prepared via grafting ferrocene onto hydroxyethylmethacrylated poly(ethylene glycol)(PEG-HEMA) block polymer narrow molecular weight distribution. The micelle did not enhance the relexation of water at all. However, after oxidation by hydrogen peroxide at acidic conditions,the micelle become bigger and showed a relaxivity comparable to clinically used CA DTPA-Gd. Furthermore, its relaxivity was sensitive to the pH of medium with higher r1at acidic pH and transition pH at3.0.This both redox and pH responsive micellar contrast have great potential in tumor imaging.