Color doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells

Perfluoropentane gas filled iron-silica nanoshells have been developed as stationary ultrasound contrast agents for marking tumors to guide surgical resection. It is critical to establish their long-term imaging efficacy, as well as biodistribution. This work shows that 500 nm Fe-SiO₂ nanoshells can be imaged by color Doppler ultrasound over the course of 10 days in Py8119 tumor bearing mice. The 500 nm nonbiodegradable SiO₂ and biodegradable Fe-SiO₂ nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with ¹¹¹In³⁺ for biodistribution studies in nu/nu mice. The majority of radioactivity was detected in the liver and kidneys following intravenous (IV) administration of nanoshells to healthy animals. By contrast, after nanoshells were injected intratumorally, most of the radioactivity remained at the injection site; however, some nanoshells escaped into circulation and were distributed similarly as those given intravenously. For intratumoral delivery of nanoshells and IV delivery to healthy animals, little difference was seen between the biodistribution of SiO₂ and biodegradable Fe-SiO₂ nanoshells. However, when nanoshells were administered IV to tumor bearing mice, a significant increase was observed in liver accumulation of SiO₂ nanoshells relative to biodegradable Fe-SiO₂ nanoshells. Both SiO₂ and Fe-SiO₂ nanoshells accumulate passively in proportion to tumor mass, during intravenous delivery of nanoshells. This is the first report of the biodistribution following intratumoral injection of any biodegradable silica particle, as well as the first report demonstrating the utility of DTPA-¹¹¹In labeling for studying silica nanoparticle biodistributions.