Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells

摘要

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.