Image-guided targeted intraarterial delivery of chemotherapy drug loaded iron oxide nanoparticles to rabbit liver cancer model.

Abstract

e14734 Background: To develop an enhanced drug delivery system to liver tumors using novel MRI traceable iron oxide nanoparticles (IONP) loaded with doxorubicin and to investigate biodistribution of deliverednanoparticle and by assessing intratumoral and normal liver tissue concentrations after targeted (IA) versus systemic (IV) administration. Methods: Paramagnetic IONP (core and hydrodynamic size of 10 nm and 23 nm, respectively) coated with amphiphilic polymers were non-covalently loaded with hydrophobic doxorubicin; whose presence was confirmed by optical absorption spectrum. VX2 liver tumors were induced in the left lobe of 12 rabbits, allowed to grow for 2 weeks to a size of 2 cm, and were subsequently divided into 2 treatment groups, each receiving 1 mg/kg body weight of doxorubicin via IONP. Group 1 received IA administration to the left hepatic artery under fluoroscopy, and Group 2 received IV administration via the marginal ear vein. Animals were sacrificed 24 hours after treatment. Tumor and liver sections were collected and iron concentrations of tumor and liver tissues were determined by the colorimetric method with iron binding 1,10-phenanthroline at 508 nm. Analysis of tissue iron concentrations in different groups was performed using a standard t-test, with p<0.05 considered significant. Results: Intratumoral and peritumoral concentrations of IONP were significantly higher 24 hours after IA administration than IV (1.54 vs 1.03 mg Fe/g , p=0.019), given at the same dosage. Additionally, 24 hours after treatment, the group receiving IA therapy showed significantly higher nanoparticle concentrations in the left hepatic lobe in comparison to the IV group (1.63 vs 1.34 mg Fe/g, p=0.0226). Conclusions: Targeted IA delivery significantly enhances intratumoral and peritumoral uptake of IONP when compared to IV. Targeted intraarterial delivery of IONP carrying doxorubincin can serve as a powerful tool in serving as a vehicle to deliver chemotherapy drugs to liver tumors. To further evaluate the potential of this drug delivery method, future studies will correlate the biodistrubution of the IONP to drug concentrations and findings on histology, imaging, tumor response.