Intratumoral delivery and therapeutic efficacy of nanoparticle-encapsulated anti-tumor siRNA following intrapulmonary administration for potential treatment of lung cancer

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.

KEYWORDS:

• Metastatic lung tumor
• siRNA-containing nanoparticle
• pulmonary drug delivery system
• B16F10
• ex vivo imaging
• survival

Acknowledgments

The authors are grateful to Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI under Grant Young Scientists (B) [number 15K19165], (B) [number 17H02178], and Scientific Research (C) [number 18K06603 and 18K12066]; the Suhara Memorial Foundation (Sapporo, Japan) under Grant; the Northern Advancement Center for Science and Technology (Sapporo, Japan) under Grant [number H29ST-ST-36]; and the Akiyama Life Science Foundation under Grant (Sapporo, Japan).