Innovative delivery of siRNA to solid tumors by super carbonate apatite

PLoS One. 2015 Mar 4;10(3):e0116022. doi: 10.1371/journal.pone.0116022. eCollection 2015.

Abstract

RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apatites / adverse effects*
  • Apatites / chemistry
  • Apatites / pharmacokinetics
  • Genetic Therapy / methods
  • HT29 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Macaca fascicularis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Neoplasms / therapy
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / therapeutic use

Substances

  • Apatites
  • Inhibitor of Apoptosis Proteins
  • RNA, Small Interfering
  • carboapatite

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research (KAKENHI) to H.Y. (No. 21390360, 30322184, 24390315). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.