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.
Highlights
Hepatocellular carcinoma (HCC) is emerging as a public health problem worldwide as the third most common cause of cancer-related deaths [1] and secondary metastatic liver tumors are even more frequent than primary hepatocellular cancer disease
This study included a total of eight rabbits; three rabbits received NPs intravenously (IV) by injections into ear vein (10 mL NP volume), three rabbits received transarterial intra-catheter (IC) injection (3 mL NP volume) and two control rabbits with liver VX2 tumors untreated with NPs
For the transarterial intra-catheter (IC) nanoparticle delivery, direct injection into liver was done with a lower volume of liquid—3 mL, again the most that can be tolerated as IC by the rabbits (Supplemental Figure S2)
Summary
Hepatocellular carcinoma (HCC) is emerging as a public health problem worldwide as the third most common cause of cancer-related deaths [1] and secondary metastatic liver tumors are even more frequent than primary hepatocellular cancer disease. We focused on the VX2 induced carcinoma implanted in the rabbit liver as a well-established model for liver tumors. In this work we have used for the first time the same two delivery approaches to introduce a novel type of core–shell nanoparticle (Supplemental Figure S1) into VX2-bearing rabbits. This nanoparticle formulation was investigated in vitro as a carrier for delivery of doxorubicin to doxorubicin-resistant cells [12] and as a source of cytotoxic reactive oxygen species following nanoparticle excitation [13]. We have included in this study an investigation of cell proliferation and apoptosis in VX2 tumors and other tissues using immunohistochemistry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
