基于热剂量的大肿瘤治疗:多部位注射可分散于肿瘤组织内的发热纳米颗粒

T. Morino, A. Ito, T. Etani, T. Naiki, N. Kawai, T. Yasui
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摘要

日本已经开发出一种基于发热纳米颗粒诱导坏死的实体癌症治疗方法。通过交变磁场照射,将磁性阳离子脂质复合颗粒(MCL颗粒)注入瘤内,诱导热杀死附近的癌细胞。在我们之前的报告中,我们已经证明了在1.36 cm 3肿瘤的单个部位注射45 mg MCL颗粒时,体内热剂量指数(J / cm 3肿瘤体积)对肿瘤消退的重要性。本研究的目的是展示多部位注射MCL颗粒治疗大于1.36 cm 3的大肿瘤的原理和效用。采用7,12-二甲基苯[a]蒽(DMBA)诱导大鼠乳腺肿瘤,肿瘤范围为2.19 ~ 3.81 cm 3。设计治疗条件,再现大鼠乳腺肿瘤各多发注射部位1.36 cm 3肿瘤治疗的产热情况。肿瘤体积除以注射部位数(cm 3 /位点)设置为接近1.36 cm 3 /位点,在多个部位施用45 mg MCL颗粒以保持注射部位之间的均匀空间。设置三种照射条件,给予1.36 cm 3肿瘤治疗的接近体内热剂量(J / cm 3)。在设计条件下的治疗导致大鼠肿瘤在治疗后21天完全消退,显示了多部位注射设计程序的理论有效性。本文描述了一个注射部位坏死肿瘤体积(立方厘米/个部位)的新概念及其在标准注射条件下45 mg-MCL /个部位的实际值,并讨论了其在临床中的应用。
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Heat Dose Based Large Tumor Treatment with Multiple Site Injections of Heat-generating Nanoparticles Dispersible within Tumor Tissue
: Solid cancer therapy based on necrosis induction with heat-generating nanoparticles has been developed in Japan. Heat was induced from intratumorally injected magnetite cationic lipid composite particles (MCL particles) by alternating magnetic field irradiations to kill cancer cells nearby located. In our previous report we have showed importance of heat dose index in vivo (J / cm 3 tumor volume) for tumor regression when 45 mg MCL particles were injected at a single site of 1.36 cm 3 tumor. Purpose of this study is to show rationale and utility of multiple site injections of MCL particles for treatment of large tumors more than 1.36 cm 3 . Rat mammary tumors were induced by 7,12-dimethylbenz [ a ] anthracene (DMBA) and tumors in range of 2.19 ~ 3.81 cm 3 were applied to treatment experiment. Treatment condition was designed to reproduce the heat generation condition of the 1.36 cm 3 tumor treatment at every multiple injection site in rat mammary tumors. Tumor volume divided by number of injection sites (cm 3 / site) was set to close to 1.36 cm 3 / site and 45 mg MCL particles were administered at multiple sites to keep even spaces among injection sites. Three irradiation conditions were set to give close heat dose in vivo (J / cm 3 ) of the 1.36 cm 3 tumor treatment. Treatment under designed conditions resulted in complete regression of rat tumors at 21 days after the treatment, showing theoretical validity of design procedures for the multiple site injections. Novel concept of necrosed tumor volume from an injection site (cm 3 / site) and its actual value under a standard injection condition of 45 mg-MCL / site were described and its use in clinic was discussed.
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