Mode of Tumor Necrosis Induction <i>in vivo</i> by Heat-generating Nanoparticles of Magnetite Cationic Lipid Composite Particles Dispersing toward Neighbor Naïve Tumor Zone and its Therapeutic Use

Novel nano-thermal ablation therapy using functionalized heat-generating nanoparticles for solid cancer treatment

“…Recently, boundary region between necrosed and alive areas was observed microscopically with mouse B16 melanoma [25]. By enlarging boundary region, tumor necrosed area was confirmed by HE staining in pink (Figure 4a,b,c).…”

“…Recently, structure and functions of the nanoparticles were investigated in detail and its therapeutic use was refined [23][24][25][26][27]. Optimum size of magnetites for heat generation under 100 kHz AMF was shown about 10 nm [23] (Figure 2a).…”

“…Then, the former name of magnetite cationic liposomes [15] was revised to magnetite cationic lipid composite particles (MCL particles) [24]. Roles of lipid components, especially a cationic lipid, were shown significant to confer several functions such as celladhesion activity [24], in vivo mobility within tumor tissue [25], tumor blood vessel disruption activity and none infiltration property toward surrounding normal tissue (unpublished result). Furthermore, theoretical background of treatment designing was constructed with heat dose index, and its advantage against temperature index was shown [26,27].…”

“…Observation area was optically checked prior to uranium acetate staining for sample preparation (e,f). Outline of tumor necrosed area was indicated with drawn line [25].…”

“…Expansion of MCL particles-distributed area by multiple irradiations was critical to induce whole tumor necrosis (Figure 3-IV). Recently, process of MCL particles expansion was investigated with tumors dissected just before the 2 nd irradiation, namely 24 hours after the 1 st irradiation [25]. One of two side by side sections were stained by Berlin blue (BB) in order to observe MCL particles.…”