Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery.

Abstract

Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA.

• Authors: Xiangyang Xie, Yanfang Yang, Wen Lin, Hui Liu, Hong Liu, Yang Yang, Ying Chen, Xudong Fu, Jianping Deng
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 136 Pg. 641-50 (Dec 01 2015) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 26492155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Small Interfering

Topics

• Animals
• Female
• Humans
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Nanostructures
• Neoplasms, Experimental (metabolism, pathology)
• RNA, Small Interfering (administration & dosage)