Color Doppler Ultrasound and Gamma Imaging of Intratumorally Injected 500 nm Iron–Silica Nanoshells

Abstract

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 non-biodegradable 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.

Synthesis and surface functionalization of silica nanoparticles for nanomedicine

“…Liberman et al have demonstrated that PFC gas filled hollow iron–silica nanoparticles can sustain a contrast signal in vivo in a tumor bearing mouse model for up to ten days after intratumoral injection [64]. In this study, 400 µg of 500 nm iron silica nanoshells were injected into the Py8119 tumor bearing Nu/Nu mice and imaged with color Doppler ultrasound.…”

“…Liberman et al functionalized the surface of 500 nm iron– silica and pure silica nanoshells with 111 In-DTPA to study nanoshell retention and accumulation in breast cancer tumors in mice [64]. The radiolabeled nanoshells were injected intravenously into tumor bearing animals, and each animal carried two Py8119 tumors on each of its rear flanks.…”

“…Intratumoral PFC filled iron-silica nanoshell imaging longevity [64]: (A–F) 50 µl of nanoshells were injected directly into Py8119 epithelial breast tumor bearing nu/nu mice and imaged by color Doppler ultrasound intermittenly over 10 days. (G) Color Doppler signal width was plotted against time to show a linear decay of signal over the course of 10 days.…”

Perfluoropentane-Encapsulated Hollow Mesoporous Prussian Blue Nanocubes for Activated Ultrasound Imaging and Photothermal Therapy of Cancer

“…Upon the heat irradiation to surrounding tissues, perfluorocarbon could be readily vaporized and converted into a steamy state, which can result in high tissue impedance mismatch and US imaging enhancement. Thus, perfluorocarbon has been demonstrated as an excellent contrast agent for the enhanced ultrasound imaging 54. NPs(HPB-PFP) have been designed and prepared for enhancing US imaging and efficient photothermal therapy of cancer both in vitro and in vivo.…”

Self-assembled targeting of cancer cells by iron(iii)-doped, silica nanoparticles

“…If one focuses on the two lower concentrations (50 and 100 μg/mL) of nanoshells, the MDA-MD-231 cells uptake four times more Fe(III)-doped, SiO 2 nanoshells than plain silica nanoshells by mass. It should be noted that the mass of the pure silica nanoshells is roughly half that of the iron doped nanoshells, 76 so the preference on a per particle basis is approximately 8×.…”