Effect of heat therapy using magnetic nanoparticles conjugated with cationic liposomes on prostate tumor in bone.
BACKGROUND
We have developed magnetite nanoparticles conjugated with cationic liposomes (MCLs) to induce intracellular hyperthermia with exposure to an alternating magnetic field (AMF). We have previously demonstrated the hyperthermic effect of MCLs against certain types of malignant tumor cells in vivo. Here, we examine the effects of MCL + AMF heat therapy on prostate cancer tissue in a bone microenvironment and on bone destruction in a rat model.


METHODS
Rat prostate cancer nodules were transplanted onto the calvaria of 6-week-old F344 male rats. MCLs were injected into the tumor which reached 7 mm in diameter, and then the animals were exposed to repeated AMF irradiation. The distribution of MCL, tumor necrosis, cell proliferation, and bone destruction in the bone microenvironment were evaluated.


RESULTS
MCL + AMF heat therapy suppressed tumor growth on the calvaria, and histologically, the induction of a necrotic mass was observed around magnetic particles in the tumor. The bone destruction index, which indicates the degree of osteolysis associated with prostate tumor growth in the bone microenvironment, was 34.8% in the MCL group and 67.2% in the control group with significant difference. However, almost half of rats were dead in this experiment.


CONCLUSIONS
MCL + AMF heat therapy suppressed tumor proliferation in the bone microenvironment, in addition to bone destruction. However, this method may exhibit side effects for central nerve system. If MCL are specifically taken into the prostate cancer cells in the bone microenvironment, this method may be useful for the treatment of bone metastatic lesions of prostate cancer.
Kawai
Noriyasu
N
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. norikawa@higashi-hosp.jp
Futakuchi
Mitsuru
M
Yoshida
Tatsuro
T
Ito
Akira
A
Sato
Shinya
S
Naiki
Taku
T
Honda
Hiroyuki
H
Shirai
Tomoyuki
T
Kohri
Kenjiro
K
D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy*; D002412:Cations; D004195:Disease Models, Animal; D055590:Electromagnetic Phenomena; D052203:Ferrosoferric Oxide / Q000627:therapeutic use*; D007036:Hypothermia, Induced / Q000379:methods*; D008081:Liposomes / Q000627:therapeutic use; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D009336:Necrosis; D009368:Neoplasm Transplantation; D010014:Osteolysis / Q000473:pathology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011827:Radiation; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D002412:Cations; D008081:Liposomes; D052203:Ferrosoferric Oxide