Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model

Abstract

The effect of hyperthermia on cervical lymph node metastasis of VX7 tongue cancer in female Japanese white rabbits was investigated. Magnetoliposomes (MLs) with a neutral surface charge and a size of 94.1 nm were used as heating mediators. MLs were injected into the tongue 20 days after tumor transplantation, and we examined whether they reached the metastatic deep cervical lymph node. The highest magnetite concentration 24 h after ML injection was detected in the lymph node, followed by tongue, spleen, blood, and liver. Rabbits were separated into three groups: group I as the control; group II with ML injection alone; and group III with ML injection and hyperthermia 24 h after ML injection, generated by applying an alternating magnetic field (118 kHz, 384 Oe) to the neck region. The hyperthermic effect was evaluated in terms of the percentage of necrosis in proportion to the metastatic tumor and the apoptotic index (AI), defined as the ratio of TUNEL-positive cells. The temperature of lymph nodes in group III reached over 44°C. The mean area of necrosis in group III was 58.0%, which was significantly higher than that in group I (19.6%) or group II (20.4%). The AI in group III was 22.9%, significantly higher than in group I (1.67%) or II (1.42%). The difference between group I and II was not statistically significant. he presence of cervical lymph node metastasis of head and neck cancer is a negative prognostic factor. The major modalities presently available for treating highly advanced head and neck cancer include surgery, radiotherapy and chemotherapy, but even the combination of all three modalities has limited efficacy. No therapeutic method has been established for cases with cervical lymph node metastasis, and the results of treatments used to date have been unsatisfactory: even with intensive radiochemothermotherapy, more than 60% of these patients die as a result of uncontrollable local progressions of the cervical lymph node metastases.1) The use of hyperthermia has generally been confined to cervical lymph node metastasis accessible with a radiofrequency system using external applicators, in combination with synergistic chemoradiotherapy. We earlier concluded that the goal of preoperative thermochemoradiotherapy is to reduce cervical lymph node metastases to surgically treatable size, and complete removal at surgery remains a critical part of treatment.2) Hyperthermia is appealing because it is a physical treatment with fewer side effects than chemotherapy and radiotherapy, and repeated treatments should be feasible without concern for cumulative toxic side effects. However, almost all recent hyperthermia methods heat not only the tumor, but also normal tissue, which is damaged by nonspecific heating. A new method to heat only the tumor and a new heating mediator for this purpose are needed. Some researchers have been investigating submicron magnetic particles as heating mediators. [3][4][5] We have recently developed magnetite particles with a cationic liposomal membrane, 'magnetite cationic liposome...

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model

“…Their data showed that liposomes about 110 nm in diameter resulted in a 17-fold higher uptake and substantially higher activity in the inflamed foot than those about 450 nm in diameter. Similar phenomena were also observed in the treatment of cervical lymph node metastases in a rabbit VX7 tongue tumor model with liposomes of 94.1 nm in diameter (Hamaguchi et al 2003). These important findings provide the basis for our selection of small-sized LADR in the present study.…”

“…Liposome size is one of the most important factors that determines the rate and extent of liposome drainage from the injection site. Small-sized liposomes, 100 nm or so in diameter, seem to achieve relatively high lymphatic uptake (Ikomi et al 1999, Moghimi & Bonnemain 1999, Oussoren & Storm 1999, Corvo et al 2000, Hamaguchi et al 2003.…”

Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles

“…Important organ such as heart, liver, spleen, lung and kidney had no magnetite accumulation by pathological examination both 24 h after MF injection and 14 days after hyperthermia. This is different from the reported (33). Fourteen days after hyperthermia, subcutaneous remnant magnetite can easily be detected through X-ray and pathological examination (Figs.…”

Heat transfer from nanoparticles: A corresponding state analysis

“…Applications include, e.g., the enhancement of cooling from structured surfaces, local heating of fluids by selective absorption from nanoparticles, with possible biomedical hyperthermia uses (6,7). Recent experiments demonstrated the possibility of reaching very high local temperatures by using laser heating of nanoparticles (8)(9)(10), even reaching the melting point of gold particles suspended in water.…”