4.7 Article

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

Journal

JOURNAL OF PERSONALIZED MEDICINE
Volume 11, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/jpm11111160

Keywords

iNaD; siRNA; microRNA; calcium phosphate; PEG blending; cancer treatment

Funding

  1. Kagoshima Shinsangyo Sousei Investment Limited Partnership [CST14001]
  2. JSPS KAKENHI [18H04059]
  3. Grants-in-Aid for Scientific Research [18H04059] Funding Source: KAKEN

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In recent years, the efficacy of sCA nanoparticle system for in vivo delivery of siRNA/miRNA has been demonstrated. A newly developed inorganic nanoparticle device (iNaD) showed similar delivery efficiency to mouse tumors compared to sCA, with reduced accumulation in the liver. iNaD loaded with tumor suppressor small RNA MIRTX resulted in improved anti-tumor effects compared to sCA loading. These findings provide new perspectives for future nanomedicine engineering.
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 mu g of miRNA, systemic administration of iNaD loaded with 0.75 mu g of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 mu g of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 mu g. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

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