Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method.

Abstract

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

• Authors: Xin Wu, Yuhki Yokoyama, Hidekazu Takahashi, Shihori Kouda, Hiroyuki Yamamoto, Jiaqi Wang, Yoshihiro Morimoto, Kazumasa Minami, Tsuyoshi Hata, Awad Shamma, Akira Inoue, Masahisa Ohtsuka, Satoshi Shibata, Shogo Kobayashi, Shuji Akai, Hirofumi Yamamoto
• Journal: Journal of personalized medicine (J Pers Med) Vol. 11 Issue 11 (Nov 08 2021) ISSN: 2075-4426 [Print] Switzerland
• PMID: 34834512 (Publication Type: Journal Article)