[Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer].
OBJECTIVE
To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer.


METHODS
Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4,500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells.


RESULTS
The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of the other groups (all P < 0.05). The growth speed of tumor in the MDL (+) group was significantly lower, and the tumor weight was significantly less than in other groups.


CONCLUSIONS
Magnetic doxorubicin liposome, as a carrier of anticancer drug, has a good targeting function toward the magnetite and has a significant anticancer effect.
Zhou
Ping-hong
PH
Zhongshan Hospital, Fudan University, Shanghai 200032, China. chow@zshospital.net
Yao
Li-qing
LQ
Qin
Xin-yu
XY
Shen
Xi-zhong
XZ
Liu
Yi-shu
YS
Lu
Wei-yue
WY
Yao
Ming
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D008280:Magnetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin