Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential.
We developed a dextran-magnetite conjugated cisplatin (DM-Cis) complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron). The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH) device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip) and placed magnets subcutaneously (sc). In group 2 we injected saline (ip) and placed magnets (sc). In group 3 we injected DM-Cis (ip) and placed a sc incision (sham). The control (group 4) received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (μm(2)) were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 μg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05) in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a magnetically-accumulated anticancer drug with hyperthermic effects.
Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 520-2192, Japan. akinaga@belle.shinga-med.ac.jp
Akinaga
A
Sonoda
Norihisa
N
Nitta
Ayumi
A
Nitta-Seko
Shinich
S
Ohta
Shigeyuki
S
Takamatsu
Yoshio
Y
Ikehata
Isamu
I
Nagano
Jun-ichiro
J
Jo
Yasuhiko
Y
Tabata
Masashi
M
Takahashi
Osamu
O
Matsui
Kiyoshi
K
Murata
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D006979:Hyperthermia, Induced / Q000379:methods; D066298:In Vitro Techniques; D055909:Magnetic Field Therapy / Q000379:methods; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry*; D050997:Nanomedicine; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D010537:Peritoneum / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D003911:Dextrans; D058185:Magnetite Nanoparticles; D058726:Nanoconjugates; D002945:Cisplatin