Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer.
Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel-embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb-c/nu/nu mice. Various concentrations of docetaxel-embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite-loaded liposome (ML)-injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43 degrees C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 microg/ml, while a docetaxel concentration > 568.5 microg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent-embedded magnetoliposomes has an anticancer effect.
Yoshida
Motohira
M
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Watanabe
Yuji
Y
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Sato
Mitsunori
M
AdMeTech Co., Ltd., Matsuyama, Ehime, Japan.
Maehara
Tsunehiro
T
Departments of Condensed Matter and Plasma Physics, Ehime University Graduate School of Science and Engineering, Matsuyama, Ehime, Japan.
Aono
Hiromichi
H
Departments of Applied Chemical Physics, Ehime University Graduate School of Science and Engineering, Matsuyama, Ehime, Japan.
Naohara
Takashi
T
Departments of Applied Chemical Physics, Ehime University Graduate School of Science and Engineering, Matsuyama, Ehime, Japan.
Hirazawa
Hideyuki
H
Departments of Applied Chemical Physics, Ehime University Graduate School of Science and Engineering, Matsuyama, Ehime, Japan.
Horiuchi
Atsushi
A
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Yukumi
Shungo
S
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Sato
Koichi
K
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Nakagawa
Hiromichi
H
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Yamamoto
Yuji
Y
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Sugishita
Hiroki
H
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Kawachi
Kanji
K
Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000077143:Docetaxel; D055590:Electromagnetic Phenomena; D005240:Feasibility Studies; D005260:Female; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel; D052203:Ferrosoferric Oxide