Inhibition of metastasis using particles that release chitosan upon radiation: A preliminary study

S. Harada, Takahiro Sato
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Abstract

This study aimed to investigate the effect of the particles releasing chitosan upon exposure to radiation on inhibition of metastasis. A 10 mL solution of water containing 0.2% weight/volume alginate, 0.1% hyaluronic acid, and 100-mg chitosan was sprayed into the vibrating solution through a stainless mesh filter (pore size: 0.8 [Formula: see text]m) using an ultrasound disintegrator, thereby generating chitosan particles. Further, [Formula: see text] particles floating in 0.1 mL normal saline were subcutaneously injected around the 4TI cells-derived tumor in the left hind legs of six-week-old male C3He/N mice. Six hours after injection, tumors were exposed to 10 Gy or 20 Gy of 100-keV soft X-ray radiation. The release of chitosan was expressed as the frequency of ruptured chitosan particles 12 h after radiation. The antimetastatic effect was confirmed by a reduction in the number of metastatic pulmonary nodules 21 days after completion of treatment. More than [Formula: see text]% of the chitosan particles released chitosan in response to radiation. The particles releasing chitosan had a prolonged antimetastatic effect when compared with the particles not releasing chitosan, thereby resulting in a significantly greater antimetastatic effect lasting for four weeks since the completion of treatment, in tumors treated with both 10 Gy and 20 Gy of radiation. Hence, particlizing chitosan could be useful in reducing metastasis in irradiated tumors.
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放射释放壳聚糖颗粒抑制肿瘤转移的初步研究
本研究旨在探讨受辐射后释放壳聚糖对肿瘤转移的抑制作用。将含有0.2%重量/体积海藻酸盐、0.1%透明质酸和100 mg壳聚糖的10 mL水溶液,通过超声波破碎机将孔径为0.8 m的不锈钢网过滤器(公式:见文)喷入振动溶液中,生成壳聚糖颗粒。在6周龄雄性C3He/N小鼠左后腿4TI细胞源性肿瘤周围皮下注射悬浮于0.1 mL生理盐水中的颗粒。注射后6小时,肿瘤分别接受10 Gy或20 Gy的100 kev软x射线照射。壳聚糖的释放量表示为辐照后12 h壳聚糖颗粒破裂的频率。治疗结束后21天,转移性肺结节数量减少,证实了抗转移效果。超过[公式:见文]%的壳聚糖颗粒释放壳聚糖响应辐射。与不释放壳聚糖的颗粒相比,释放壳聚糖的颗粒具有较长的抗转移作用,因此在接受10 Gy和20 Gy放射治疗的肿瘤中,在治疗结束后的四周内,其抗转移作用明显更大。因此,壳聚糖颗粒化可能有助于减少放射肿瘤的转移。
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