Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles.
We previously investigated the utility of μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.|Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Itaru
I
Sato
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
Masanari
M
Umemura
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Kenji
K
Mitsudo
Department of Orthopedic Surgery, Yokohama Touhoukai Hospital, Yokohama, 236-0031, Japan.
Hidenobu
H
Fukumura
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
Jeong-Hwan
JH
Kim
Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, 240-8501, Japan.
Yujiro
Y
Hoshino
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Hideyuki
H
Nakashima
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Mitomu
M
Kioi
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.|Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Rina
R
Nakakaji
Department of Physiology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Motohiko
M
Sato
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
Takayuki
T
Fujita
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
Utako
U
Yokoyama
Tsurumi University School of Dental Medicine, Tsurumi, 230-8501, Japan.
Satoshi
S
Okumura
Department of Pathology, Jichi Medical Universityepartment of Pathology, Tochigi, 329-2111, Japan.
Hisashi
H
Oshiro
Advanced Applied Science Department, Research Laboratory, IHI Corporation, Yokohama, 235-8501, Japan.
Haruki
H
Eguchi
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.
Iwai
I
Tohnai
Cardiovascular Research Institute, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
Yoshihiro
Y
Ishikawa
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004358:Drug Therapy / Q000379:methods*; D006979:Hyperthermia, Induced / Q000379:methods*; D058085:Iron Compounds / Q000627:therapeutic use*; D053758:Nanoparticles / Q000627:therapeutic use*; D011817:Rabbits; D014062:Tongue Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D058085:Iron Compounds; C000625957:mu-oxo N,N'- bis(salicylidene)ethylenediamine iron