Study On The Ultra-Small Fe₃O₄ Nanoprobes Targeting To Tumor Angiogenesis

Tumor molecular imaging has received enormous attention. Developing ultrasensitive broad-spectrum molecular imaging probes for the accurate diagnoses of malignant solid tumors still faces great challenges. In this thesis, we report a novel approach for the synthesis of angiogenesis-target ultra-small Fe₃O₄ nanoprobes by covalently conjugating c?RGDyK? peptide to PEGylated ultra-small Fe₃O₄ nanoparticles and apply it as magnetic resonance imaging ?MRI? positive contrast agent to realize active-target T₁-weighted imaging of tumors in vivo.Angiogenesis-target ultra-small Fe₃O₄ nanoprobes possesses optimal relaxation properties. It exhibited high r₁ of 7.74 mM^-1s^-1 and ultralow r₂/r₁ of 2.8 at 3 T, reflecting their excellent T₁ contrast effect at clinically relevant magnetic field. High angiogenesis-target specificity together with favorable biocompatibility and strong ability to resist against non-specific uptake were evaluated through in vitro studies. In vivo experiments revealed its excellent targeting ability as well as the efficient T₁ contrast on multiple types of mice tumor models ?subcutaneously xenografted tumor, metastases and orthotopic tumor?, allowing the tumor imaging with higher spatial definition in a very short scan time. Owing to its outstanding performance for tumor imaging, angiogenesis-target ultra-small Fe₃O₄ nanoprobes possesses great potential as ultrasensitive broad-spectrum molecular imaging probes for solid tumor accurate diagnoses and the assessments of post therapeutic effect.