Anti-cancer effect of hyperthermia on breast cancer by magnetite nanoparticle-loaded anti-HER2 immunoliposomes.
BACKGROUND
We have constructed anti-HER2 immunoliposomes containing magnetite nanoparticles (HML) that generate heat in an alternating magnetic field (AMF). The effective targeting and cytocidal abilities of HML have been achieved using cell culture models. This study aimed to investigate feasibility of this modality for breast cancer treatment using tumor-bearing mouse models.


METHODS
The subcutaneous cancer nodules of BT474 (high HER2 expression) or SKOV3 (low HER2 expression) cells in nude mice were employed as models. HMLs were injected into these cancer nodules and were then exposed to an AMF for 30 min twice at 24 h intervals. Accumulation of magnetite and tumor growth rates were examined. Histological findings of the thermal effect were also examined.


RESULTS
HMLs accumulated in only BT474 tumors. The tumor temperature increased to 45 degrees C whereas the body temperature remained at around 38 degrees C. Tumor regression was observed in the hyperthermic group and was sustained for 10 weeks after hyperthermia.


CONCLUSIONS
These results suggest that hyperthermia using HML is an effective and specific therapy for breast cancer overexpressing HER2. This therapy may provide an alternative way to treat recurrent cancer refractory to other modalities.
Kikumori
Toyone
T
Department of Breast and Endocrine Surgery, Nagoya University Hospital, Showaku, Nagoya, Japan. kikumori@med.nagoya-u.ac.jp
Kobayashi
Takeshi
T
Sawaki
Masataka
M
Imai
Tsuneo
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D004574:Electromagnetic Fields; D005260:Female; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D006979:Hyperthermia, Induced; D008081:Liposomes; D008280:Magnetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D052203:Ferrosoferric Oxide; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab