Intratumoral delivery and therapeutic efficacy of nanoparticle-encapsulated anti-tumor siRNA following intrapulmonary administration for potential treatment of lung cancer
Intratumoral delivery and therapeutic efficacy of nanoparticle-encapsulated anti-tumor siRNA following intrapulmonary administration for potential treatment of lung cancer
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DOI：
10.1080/10837450.2019.1633345
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发表时间：
2019-06
影响因子：
3.4
通讯作者：
Yukimune Kanehira;K. Togami;K. Ishizawa;S. Sato;H. Tada;S. Chono
中科院分区：
文献类型：
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作者：
Yukimune Kanehira;K. Togami;K. Ishizawa;S. Sato;H. Tada;S. Chono
摘要本研究评价了含抗肿瘤小干扰核糖核酸(SiRNA)纳米粒肺内给药对小鼠肺转移瘤的给药效率和抗肿瘤作用。使用Liquid MicroSprayer®将荧光标记的含有siRNA的纳米颗粒注射到由小鼠黑色素瘤细胞系B16F10诱导的转移性肺肿瘤小鼠体内。肺内注射含有siRNA的纳米颗粒后，全肺和肿瘤区域的荧光信号比静脉注射后更强。肺内注射含有针对MDM2、c-Myc和血管内皮生长因子(VEGF)的siRNA的纳米颗粒显著提高了转移性肺癌小鼠的存活率并延长了存活期。此外，肺内或静脉给药后，全身毒性的标志物白介素6和白介素12的活性水平与未治疗时相似。这些结果表明，含有抗肿瘤siRNA的纳米颗粒被高效且特异性地输送到肿瘤细胞，有效地沉默了肺转移中的癌基因，而没有任何明显的全身毒性。
Abstract This study evaluated the delivery efficiency and antitumor effects of the intrapulmonary administration of antitumor small interfering ribonucleic acid (siRNA)-containing nanoparticles to mice with metastatic lung tumor. Fluorescence-labeled, siRNA-containing nanoparticles were administered using Liquid MicroSprayer® to mice with metastatic lung tumors induced by the murine melanoma cell line B16F10. Fluorescent signals in the whole lung and in the tumor region following the intrapulmonary administration of siRNA-containing nanoparticles were stronger than those following intravenous administration. The intrapulmonary administration of nanoparticles containing a mixture of siRNA against MDM2, c-Myc, and vascular endothelial growth factor (VEGF) significantly improved survival and prolonged the survival of mice with metastatic lung tumor. In addition, after the intrapulmonary or intravenous administration of the mixture, the activity levels of interleukin-6 and -12, markers of systemic toxicity, were similar to those of nontreatment. These results indicate that the antitumor siRNA-containing nanoparticles were delivered efficiently and specifically to tumor cells, effectively silencing the oncogenes in the lung metastasis without any significant systemic toxicity.