Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 146, Issue -, Pages 607-615Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2016.07.002
Keywords
Thermosensitive release; Magnetic guidance; Cell-penetrating peptides; siRNA delivery; Liposomes
Funding
- National Natural Science Foundation of China [81402874]
- PUMC Youth Fund
- Fundamental Research Funds for the Central Universities [3332015139]
- Beijing Natural Science Foundation of China [7162135]
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Due to the absence of effective in vivo delivery systems, the employment of small interfering RNA (siRNA) in the clinic has been hindered. Here, we describe a novel siRNA targeting system that combines features of biological (cell-permeable peptides, CPPs) and physical (magnetic) siRNA targeting for use in magnetic hyperthermia-triggered release. A siRNA-CPPs conjugate (siRNA-CPPs) was loaded into thermal and magnetic dual-responsive liposomes (TML) (siRNA-CPPsiTML), and in vitro siRNA-CPPs thermosensitive release activity, targeted cellular uptake, gene silencing efficiency, in vivo targeted delivery and in vivo antitumor activity were determined. The results demonstrated that siRNA-CPPs/TML exhibited good physicochemical properties, effective cellular uptake, endosomal escape and a significant gene silencing efficiency in MCF-7 cells in vitro. Additionally, in the in vivo study, siRNA-CPPs/TML under an alternating current (AC) magnetic field displayed a superior in vivo targeted delivery efficacy, antitumor efficacy and gene silencing efficiency in a MCF-7 xenograft murine model. In conclusion, the application of siRNA-CPP5/TML under an AC magnetic field represents a new strategy for the selective and efficient delivery of siRNA. (C) 2016 Elsevier B.V. All rights reserved.
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