Experimental Study Of Magnetic Doxorubicin Nano-liposomes Targeted Therapy In Nude Mice With Colorectal Cancer

Targeting Therapy of Magnetic Doxorubicin Nano-Liposome in Nude Mice Bearing Colon CancerIt is well recognized that traditional systemic chemotherapy has the low therapeutic index and poor patient's compliance. Targeting therapy for solid tumors, using specific carriers to locate anticancer drugs selectively to solid tumors under specific guiding mechanism, may increase the drug concentration in the required sites. Such an approach would dramatically increase the anticancer drugs' therapeutic efficacy, reduce the drugs' toxic side effects and increase the patient's compliance. The present study investigated the magnetic nano-liposome designed to act as doxorubicin (DOX) carrier, which could be effectively delivered to solid tumors via intravenous administration. Magnetic doxorubicin nano-liposome (MDNL) was prepared by the reverse-phase evaporation method. We studied the response of MDNL to the magnetite both out of and within the body, investigated the biological distribution of the MDNL in the nude mice bearing colon cancer. The therapeutic effect of MDNL to nude mice bearing colon cancer was also intensively studied. The results showed that: (1) The particle size of MDNL was 230nm, the concentration of DOX in MDNL was 300μg/ml, and the entrapment rate of DOX was about 25%. Different lipid ratio, drug lipid ratio, organic solvent and ratio of water/oil phase may influence the particle size of MDNL and the entrapment rate of DOX. The leakage rate of DOX in MDNL was very low within the preservative 8 hours under 40C after preparation. (2) MDNL had a good response to the magnetite both out of and within the body. Administration of MDNL under magnetic field could be used to deliver DOX effectively to the targeted site, increasing DOX concentration in the tumor and decreasing DOX concentration in the heartand the kidney. (3) Treatment with MDNL via intravenous administration under magnetic force implanted in the center of the tumor showed significant greater anticancer activity than any other modalitity.The present results suggested that as a new carrier of DOX, MDNL could be used to deliver DOX effectively to the tumor implanted with a permanent magnet, increasing DOX concentration in the tumor and decreasing the side effects of the heart and the kidney. This new treatment approach involving a combination of magnet implantion in the center of the tumor and intravenous administration of MDNL could effectively control the tumor growth. In summary, our study indicated that magnetic nano-liposome, as an carrier of anticancer drug, had a wide window of opportunity to achieve even anticancer effects in clinical settings. Targeting therapy could be a novel approach to the cancer treatment.