Distribution of iron oxide core-titanium dioxide shell nanoparticles in VX2 tumor bearing rabbits introduced by two different delivery modalities

Tamer Refaat, Derek West, Samar El Achy, Vamsi Parimi, Jasmine May, Lun Xin, Kathleen R. Harris, William Liu, Michael Beau Wanzer, Lydia Finney, Evan Maxey, Stefan Vogt, Reed A. Omary, Daniele Procissi, Andrew C. Larson, Tatjana Paunesku, Gayle E. Woloschak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

Original languageEnglish (US)
Article number143
JournalNanomaterials
Volume6
Issue number8
DOIs
StatePublished - Aug 2016

Funding

This study was supported by NIH grants RO1EB002100 and U54CA151880 and training grant R25CA132822. Work at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Contract No. DE-AC02-06CH11357. Peptide synthesis was performed in the Analytical BioNanoTechnology Equipment Core of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility. Immunohistochemistry, H&E staining and Nanozoomer microscopy were done by Northwestern University Pathology core.

Keywords

  • Core-shell nanoparticle
  • Rabbit VX2 liver cancer model
  • Transarterial intra-catheter delivery

ASJC Scopus subject areas

  • General Chemical Engineering
  • General Materials Science

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