Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.
OBJECTIVE
To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) 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 LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated.


RESULTS
Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) 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 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) 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 Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) 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.


CONCLUSIONS
Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) 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.
Wang
Zi-Yu
ZY
School of Basic Medical Sciences, Southeast University, Nanjing, Jiangsu Province, China.
Song
Jian
J
Zhang
Dong-Sheng
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D006979:Hyperthermia, Induced; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008280:Magnetics; D008297:Male; D008422:Materials Testing; D008516:Medicine, Chinese Traditional; D051379:Mice; D008819:Mice, Nude; D054118:Nanospheres / Q000737:chemistry / Q000627:therapeutic use; D010087:Oxides / Q000737:chemistry / Q000627:therapeutic use; D011897:Random Allocation; D013552:Swine; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D001152:Arsenicals; D001672:Biocompatible Materials; D005290:Ferric Compounds; D010087:Oxides; C000499:ferric oxide; D000077237:Arsenic Trioxide