Innovative delivery of siRNA to solid tumors by super carbonate apatite

Xin Wu, Hirofumi Yamamoto, Hiroyuki Nakanishi, Yuki Yamamoto, Akira Inoue, Mitsuyoshi Tei, Hajime Hirose, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Sharif Hossain, Toshihiro Akaike, Nariaki Matsuura, Yuichiro Doki, Masaki Mori

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17 Citations (Scopus)

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.

Original languageEnglish
Article numbere0116022
JournalPloS one
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 4 2015
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Wu, X., Yamamoto, H., Nakanishi, H., Yamamoto, Y., Inoue, A., Tei, M., ... Mori, M. (2015). Innovative delivery of siRNA to solid tumors by super carbonate apatite. PloS one, 10(3), [e0116022]. https://doi.org/10.1371/journal.pone.0116022