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

Innovative delivery of siRNA to solid tumors by super carbonate apatite.

Author information

1
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
2
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
3
Nakanishi Gastroenterological Research Institute, Sakai, Japan.
4
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan; Biomaterials Center for Regenerative Medical Engineering, Foundation for Advancement of International Science, Tsukuba, Japan.
5
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.

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.

PMID:
25738937
PMCID:
PMC4349808
DOI:
10.1371/journal.pone.0116022
[Indexed for MEDLINE]
Free PMC Article

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