TY - JOUR
T1 - Innovative delivery of siRNA to solid tumors by super carbonate apatite
AU - Wu, Xin
AU - Yamamoto, Hirofumi
AU - Nakanishi, Hiroyuki
AU - Yamamoto, Yuki
AU - Inoue, Akira
AU - Tei, Mitsuyoshi
AU - Hirose, Hajime
AU - Uemura, Mamoru
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Hossain, Sharif
AU - Akaike, Toshihiro
AU - Matsuura, Nariaki
AU - Doki, Yuichiro
AU - Mori, Masaki
N1 - Publisher Copyright:
© 2015 Wu et al.
PY - 2015/3/4
Y1 - 2015/3/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0116022
DO - 10.1371/journal.pone.0116022
M3 - Article
C2 - 25738937
AN - SCOPUS:84924308496
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 3
M1 - e0116022
ER -