Innovative delivery of siRNA to solid tumors by super carbonate apatite

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 usi...

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Bibliographic Details
Published in:PloS one 2015-03, Vol.10 (3), p.e0116022-e0116022
Main Authors: Wu, Xin, Yamamoto, Hirofumi, Nakanishi, Hiroyuki, Yamamoto, Yuki, Inoue, Akira, Tei, Mitsuyoshi, Hirose, Hajime, Uemura, Mamoru, Nishimura, Junichi, Hata, Taishi, Takemasa, Ichiro, Mizushima, Tsunekazu, Hossain, Sharif, Akaike, Toshihiro, Matsuura, Nariaki, Doki, Yuichiro, Mori, Masaki
Format: Article
Language:English
Subjects:
Animals
Apatite
Apatites
Apatites - adverse effects
Apatites - chemistry
Apatites - pharmacokinetics
Apoptosis
Biomedical materials
Cancer therapies
Carbonates
Care and treatment
Clinical trials
Cytoplasm
Engineering
Gene expression
Genetic aspects
Genetic Therapy - methods
Health aspects
HT29 Cells
Humans
Inhibitor of Apoptosis Proteins - genetics
Macaca fascicularis
Medical research
Medicine
Mice
Mice, Inbred BALB C
Mice, Nude
Microscopy
Monkeys
Nanoparticles
Nanoparticles - adverse effects
Nanoparticles - chemistry
Nanotechnology
Neoplasms - therapy
pH effects
Physiological aspects
Polyethylene glycol
Quantum dots
Reagents
Ribonucleic acid
RNA
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - therapeutic use
RNA-mediated interference
siRNA
Solid tumors
Surgery
Survivin
Tumor cells
Tumors
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0116022