Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 28, 2009; 15(24): 2995-3002
Published online Jun 28, 2009. doi: 10.3748/wjg.15.2995
Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells
Zi-Yu Wang, Jian Song, Dong-Sheng Zhang
Zi-Yu Wang, School of Clinical Medicine, Southeast University, Nanjing 210009, China; School of Basic Medical Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, Jiangsu Province, China
Jian Song, Dong-Sheng Zhang, School of Basic Medical Sciences, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Wang ZY and Song J designed the study, performed the experiments, analyzed the data, and wrote the paper; Zhang DS supervised the study.
Correspondence to: Dong-Sheng Zhang, School of Basic Medical Sciences, Southeast University, Nanjing 210009, Jiangsu Province, China. b7712900@jlonline.com
Telephone: +86-25-83272502
Received: December 24, 2008
Revised: May 11, 2009
Accepted: May 18, 2009
Published online: June 28, 2009
Abstract

AIM: To study the methods of preparing the magnetic nano-microspheres of Fe2O3 and As2O3/Fe2O3 complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH).

METHODS: Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD50 along with other in vivo tests were performed to evaluate the Fe2O3 microsphere biocompatibility. The inhibition ratio of tumors after Fe2O3 and As2O3/Fe2O3 injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated.

RESULTS: Fe2O3 and As2O3/Fe2O3 particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51°C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe2O3 microspheres are a new kind of biomaterial without cytotoxic effects. The LD50 of both Fe2O3 and As2O3/Fe2O3 in mice was higher than 5 g/kg. One to four weeks after Fe2O3 and As2O3/Fe2O3 complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe2O3 and As2O3/Fe2O3 groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not.

CONCLUSION: Fe2O3 and As2O3/Fe2O3 complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.

Keywords: Liver cancer; Magnetic fluid hyperthermia; Nanoparticle; As2O3