Influence of copper nanoparticles on the growth characteristics of tumors in white outbreed rats

P. Kachesova, I. Goroshinskaya, G. Zhukova, E. Shalashnaya, I. A. Kaplieva, V. B. Borodulin
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Abstract

Purpose of the study. To study the effect of copper nanoparticles on the characteristics of the transplanted tumors of rats, as well as to assess the dependence of the effect on the method of administration of nanoparticles.Materials and methods. In experiments on 163 white outbred male rats, 160–200 g, the size and growth rate of transplanted sarcoma 45 and Pliss' lymphosarcoma were determined in dynamics when a suspension of copper nanoparticles in physiological saline was injected intratumorally or intraperitoneally in a total dose of 10 mg/kg. Nanoparticles had a "core-shell" structure with variable diameter in the range of 30–75 nm. Contrary to other researches, we started the exposure to metal nanoparticles only when the tumors had become visible and had grown up to the sizes at which their spontaneous regression was unlikely.Results. In most animals (up to 89 %), significant antitumor effects of copper nanoparticles were obtained up to complete regression of tumors with large volumes. The effects of nanodispersed copper differed in tumors with different histological structures and growth patterns. Experiments on a transplantable, slowly growing sarcoma 45 showed a decrease in the specific tumor growth rate after a single injection of nanoparticles (1.25 mg/kg), a decrease in tumor size could be observed after 4 injections (a total dose of 5 mg/kg). In the case of a rapidly growing tumor model (Pliss' lymphosarcoma), a decrease in tumor growth rates caused by copper nanoparticles occurred at later stages of exposure, after the animals received nanoparticles at a total dose of 5–10 mg/kg. The efficiency depended on the approach of nanoparticles injection.Conclusion. In case of sarcoma 45, intraperitoneal injection of copper nanoparticles was more effective than intratumoral one, while in rats with Pliss' lymphosarcoma intratumoral injection of the nanoparticles had some advantages. The results indicate that nanodispersed copper is a promising antitumor factor. The mechanisms of regression of large transplanted tumors under the influence of copper nanoparticles are discussed.
铜纳米颗粒对白色异种大鼠肿瘤生长特性的影响
研究目的:目的:研究铜纳米颗粒对大鼠移植肿瘤特性的影响,并评价其对纳米颗粒给药方式的依赖性。材料和方法。以163只160 ~ 200 g白种雄性大鼠为实验对象,以10 mg/kg的总剂量在生理盐水中注入铜纳米颗粒悬浮液,动态观察移植肉瘤45和Pliss淋巴肉瘤的大小和生长速率。纳米颗粒具有“核壳”结构,直径在30 ~ 75 nm范围内变化。与其他研究相反,我们开始接触金属纳米粒子时,肿瘤已经可见,并且已经长到不太可能自发消退的程度。在大多数动物(高达89%)中,铜纳米颗粒具有显著的抗肿瘤作用,直至大体积肿瘤完全消退。纳米分散铜在不同组织结构和生长方式的肿瘤中的作用不同。对可移植、生长缓慢的肉瘤45的实验表明,单次注射纳米颗粒(1.25 mg/kg)后,肿瘤特定生长速率降低,注射4次(总剂量为5 mg/kg)后,肿瘤体积减小。在快速生长的肿瘤模型(Pliss淋巴肉瘤)中,铜纳米颗粒引起的肿瘤生长速度下降发生在暴露的后期,即动物接受总剂量为5-10 mg/kg的纳米颗粒后。纳米颗粒的注射方式与注射效率有关。对于45型肉瘤,腹腔注射纳米铜颗粒比瘤内注射更有效,而对于Pliss淋巴肉瘤,瘤内注射纳米铜颗粒有一定优势。结果表明,纳米分散铜是一种很有前途的抗肿瘤因子。讨论了铜纳米粒子对大移植肿瘤消退的影响机制。
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