Innovative delivery of siRNA to solid tumors by super carbonate apatite

PloS One
Xin WuMasaki Mori

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.

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Citations

Dec 10, 2015·IET Nanobiotechnology·Neha Mehrotra, Ravi Mani Tripathi
Oct 13, 2016·Frontiers in Pharmacology·Jana MerhautovaOndrej Slaby
Mar 18, 2017·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Hugh Colvin, Masaki Mori
Dec 13, 2018·Japanese Journal of Clinical Oncology·Norikatsu MiyoshiMasaki Mori
Feb 19, 2020·British Journal of Cancer·Yoshihiro MorimotoHirofumi Yamamoto
Sep 11, 2020·Molecular Therapy. Nucleic Acids·Masayo AokiKazuaki Takabe
Mar 14, 2021·Life Sciences·Md Abdus SubhanVladimir P Torchilin

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Methods Mentioned

BETA
transfection
atomic force microscopy
dynamic
AFM
flow cytometry
confocal microscopy
flow
fluorescence microscopy
X-ray
Dynamic Light-Scattering

Software Mentioned

VetScan
BD FACS Diva
H1C
BZ
JMP10

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