Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters.
To control the growth of primary tumors effectively with systemic chemotherapy, we recently developed intravenously administered small-sized magnetic liposomes as an anticancer drug carrier. We previously reported that intravenously administered magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) effectively delivered ADR to the target site where a permanent magnet was implanted. In the present study, the therapeutic efficacy of this novel treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, was further evaluated by comparing tumor growth rates among different administration modalities and by histological examination of treated tumors. Small-sized magnetic ADR liposomes with a mean diameter of 146 nm were prepared by the reverse-phase evaporation method. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. One day prior to the animal study, either a permanent magnet (with magnetic force) or non-magnetic alloy (without magnetic force) was implanted in the center of the tumors. Treatment with magnetic ADR liposomes under magnetic force showed significantly greater antitumor activity than intravenous administration of ADR solution or that of magnetic ADR liposomes without magnetic force. ADR administered as magnetic liposomes eliminated weight loss of hamsters, one of the side effects produced by ADR. Interestingly, magnetic liposomes (without incorporated ADR) given under magnetic force also suppressed the tumor growth. The selective accumulation of magnetite particles in the tumor blood vessels was observed by histological examination. These results suggest that this systemic chemotherapy can effectively control the primary tumor without significant side effects, due to the targeting of magnetic ADR liposomes.
Kubo
T
T
Department of Orthopaedic Surgery, Faculty of Medicine, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan. kubo@mcai.med.hiroshima-u.ac.jp
Sugita
T
T
Shimose
S
S
Nitta
Y
Y
Ikuta
Y
Y
Murakami
T
T
D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D052203:Ferrosoferric Oxide; D007262:Infusions, Intravenous; D007501:Iron / Q000008:administration & dosage; D008081:Liposomes; D008280:Magnetics; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage
D004337:Drug Carriers; D008081:Liposomes; D010087:Oxides; D004317:Doxorubicin; D007501:Iron; D052203:Ferrosoferric Oxide