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Purpose:Brain glioma is the most common primary intracranial tumor with high recurrence rate and high death rate.MRI is the most important early diagnosis tool for gliomas.Super paramagnetic iron oxide nanoparticles(SPIONs),a T2 contrast agent,have less efficient magnetic resonance imaging effect because of the weak ability to penetrate the blood brain barrier.Previous studies have look at different ligands bound on the surface of the SPIONs to enhance their targeting ability.However,the contrast effect is still not ideal;What kind of effect the Polyethylene glycol(PEG),which can increase the circulation time,the dispersion and stability of nanoprobes in body fluid,have on the uptake of nanoprobes by brain glioma has not been reported.Therefore,we designed a kind of FA and CTX dual-targeting nanoprobes with three different molecular weight of PEG(2K vs 3.5K vs 5k).Methods: FA and CTX modified dual-target SPIONs with different molecular weight of PEG were prepared and characterized.Uptake of the glioma cells on nanoprobes(blocking or non-blocking receptor)and MRI,near infrared imaging,laser confocal imaging of nude mice wearing brain glioma showed that the combination of dual target improves the targeting specificity of SPIONs.In addition,we also explored the toxicity and the distribution of nanoprobes.Results: The uptake experiments of glioma cells(blocking or non-blocking receptor)revealed that dual-targeting nanoparticles are more internalized by glioma cells due to the synergistic targeting effect.More importantly,dual-targeting nanoprobes with different molecular weight of PEG exhibited differentiated targeting specificity.What is more,nanoprobes with PEG2K exhibit most effective intake effect for gliomas.The results of in vivo magnetic resonance imaging,near infrared imaging and laser confocal imaging are consistent with the results of in vitro experiments.Conclusion:The experimental results show the FA and CTX modified dual-target SPIONs with PEG2k as MRI contrast agent with low toxicity,distinct MR imaging and excellent targeting for glioma.