Synthesis Of Tumor Targeting Superparamagnetic Iron Oxide Nanoparticles As MRI Contrast Agents And Its Application In Liver Cancer MRI Imaging

Liver cancer has become one of the most common cancers in China,and it accounts for the highest proportion of cancer deaths among male Chinese,which seriously jeopardizes the health of our people.The early diagnosis of liver cancer plays an important role in improving the therapeutic effect in the later stage and improving the survival rate of patients.As an emerging medical imaging technology,magnetic resonance imaging?MRI?has many advantages such as high diagnostic compliance,non-invasiveness,and is very suitable for clinical diagnosis of liver cancer.However,for tumor tissues with a diameter less than 1 cm,MRI has a problem that the difference between the lesion site and the normal liver tissue signal is not obvious.It is necessary to use a contrast agent to improve the signal difference between the lesion site and the normal tissue.Superparamagnetic nano-iron oxide particles?SPION?,as a T2 contrast agent for MRI,possesses good biocompatibility,low toxicity,high relaxation rate,and passive targeting of tumor sites.Through functionalized modification,SPION can achieve active targeting of liver cancer,which is a MRI contrast agent with great development potentialities for liver cancer.In this paper,a SPION with active targeting and passive targeting of tumors was prepared,the ability of tumor targeting and liver cancer MRI imaging were evaluated by cell realization and animal model experiments.The main contents of this paper are as follows:?1?Hydrophilic SPION coated with HES with a particle size of 38 nm and a potential of-6 mV was prepared.The results of dynamic light scattering measurement showed that the prepared SPION particle size distribution was narrow and evenly distributed in water;This SPION also has high solubility and can be stable for a long time.Two poly-lysine polymers with acidic response polypeptide pHLIP:PDL-?PEG?₂₄-ACP?pHLIP N-terminal linking?and pHLIPx-?PEG?₂₄-PDL?pHLIP C-terminal linking?polymers were synthesized and isolated and purified,and their structures were confirmed by UV and fluorescence spectroscopy.The pH response ability of these polymers was verified by the circular dichroism spectroscopy.SPION clusters were successfully assembled by mixed the synthesized polymers with the hydrophilic SPION.The DLS results show that the particle size of the obtained SPION clusters can be precisely controlled by controlling the amount of the polymer,and the assembled SPION is uniformly distributed in water.The TEM results show that the distribution of the SPION clusters is narrow,and the morphology is complete and stable.?2?The acidic response ability of the prepared SPION clusters was investigated by cell experiments.The results showed that the targeting group played a good pH response ability,and the PDL-?PEG?₂₄-ACP assembled SPION clusters had a better pH response ability.?3?The transverse relaxation rate of SPION was investigated.The results show that the relaxation rate of the hydrophilic HES-SPION is 55.367 mM-1*s-1,and the relaxation rate is positively correlated with the particle size of SPION.The successful establishment of orthotopic liver cancer model was confirmed by tissue observation and section observation.The prepared SPION clusters was performed for MRI imaging of mouse orthotopic liver cancer.The results show that different SPIONs have certain background T2 contrast effects,and only SPION clusters with pH response peptides has the ability of dynamic MRI imaging of tumors,which has potential practical value for accurate diagnosis of liver cancer tumors less than 1 cm in diameter.