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 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.
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.
Xin
X
Wu
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hirofumi
H
Yamamoto
Nakanishi Gastroenterological Research Institute, Sakai, Japan.
Hiroyuki
H
Nakanishi
Nakanishi Gastroenterological Research Institute, Sakai, Japan.
Yuki
Y
Yamamoto
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Akira
A
Inoue
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Mitsuyoshi
M
Tei
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hajime
H
Hirose
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Mamoru
M
Uemura
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Junichi
J
Nishimura
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Taishi
T
Hata
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Ichiro
I
Takemasa
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Tsunekazu
T
Mizushima
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.
Sharif
S
Hossain
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.
Toshihiro
T
Akaike
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Nariaki
N
Matsuura
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Yuichiro
Y
Doki
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Masaki
M
Mori
D000818:Animals; D001031:Apatites / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D015316:Genetic Therapy / Q000379:methods; D019073:HT29 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use
D001031:Apatites; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; C030782:carboapatite