Systemic delivery of siRNA by T7 peptide modified core-shell nanoparticles for targeted therapy of breast cancer.

Abstract

Systemic delivery of siRNA is the most challenging step to transfer RNAi to clinical application for breast cancer therapy. In this study, the tumor targeted, T7 peptide modified core-shell nanoparticles (named as T7-LPC/siRNA NPs) were constructed to achieve effective systemic delivery of siRNA. The core-shell structure of T7-LPC/siRNA NPs enables them to encapsulate siRNA in the core and protect it from RNase degradation during circulation. In vitro cellular uptake and gene silencing experiments demonstrated that T7-LPC/siEGFR NPs could deliver EGFR siRNA into breast cancer cells through receptor mediated endocytosis and effectively down-regulate the EGFR expression. In vivo distribution study proved the T7-LPC/siRNA NPs could deliver fluorescence labeled siRNA to the tumor site more efficiently than the non-targeted PEG-LPC/siRNA NPs after intravenous administration. Furthermore, the experiments of in vivo tumor therapy confirmed that intravenous administration of T7-LPC/siEGFR NPs led to an effective EGFR down-regulation and an obvious inhibition of breast tumor growth, with little activation of immune responses and negligible body weight loss. These results suggested that T7-LPC/siRNA NPs could be an effective and safe systemic siRNA delivery system for RNAi-based breast cancer therapy.

• Authors: Min-Zhi Yu, Wen-Hao Pang, Ting Yang, Jian-Cheng Wang, Lin Wei, Chong Qiu, Yi-Fan Wu, Wei-Zhong Liu, Wei Wei, Xi-Ying Guo, Qiang Zhang
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 92 Pg. 39-48 (Sep 20 2016) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 27355138 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type IV
• Interleukin-6
• Peptide Fragments
• Phosphatidylethanolamines
• RNA, Small Interfering
• interleukin-6, mouse
• tumstatin (74-98)
• 1,2-distearoylphosphatidylethanolamine
• Polyethylene Glycols
• Interferon-gamma
• ErbB Receptors

Topics

• Animals
• Breast Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cell Proliferation (drug effects)
• Collagen Type IV (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• ErbB Receptors (genetics, metabolism)
• Female
• Humans
• Interferon-gamma (blood)
• Interleukin-6 (blood)
• MCF-7 Cells
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (administration & dosage, chemistry, therapeutic use)
• Peptide Fragments (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Phosphatidylethanolamines (chemistry)
• Polyethylene Glycols (chemistry)
• RNA Interference
• RNA, Small Interfering (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Tissue Distribution
• Tumor Burden (drug effects)