Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy.

Abstract

Developing safe and effective carriers of small interference RNA (siRNA) is a significant demand for the systemic delivery of siRNA. In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytometry showed that LDL-coupled nanoparticles were more easily taken up than Dox-SCS-NPs. Results of confocal microscopy and reverse transcription-PCR revealed the highly efficient uptake of siRNA and the decrease in mdr1 mRNA expression. LDL-coupled nanoparticles protected siRNA from macrophage phagocytosis by dynamic observation using live cell station. In vivo tumor-targeting suggested that Cy7-labelled Dox-LDL-SCS-NPs were markedly accumulated in an analyzed in situ liver tumor model. Results indicated that LDL-SCS-NPs were effective tumor-targeting vectors and that the preparation form may provide a new strategy for co-delivering siRNA and antitumor drugs.

• Authors: Qiao-ling Zhu, Yi Zhou, Min Guan, Xiao-feng Zhou, Shu-di Yang, Yang Liu, Wei-liang Chen, Chun-ge Zhang, Zhi-qiang Yuan, Chun Liu, Ai-jun Zhu, Xue-nong Zhang
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 22 Pg. 5965-76 (Jul 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24768047 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antibiotics, Antineoplastic
• Drug Carriers
• Lipoproteins, LDL
• N-succinyl-chitosan
• RNA, Small Interfering
• Doxorubicin
• Chitosan

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Animals
• Antibiotics, Antineoplastic (administration & dosage)
• Chitosan (chemistry)
• Doxorubicin (administration & dosage)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Resistance, Multiple
• Female
• Hep G2 Cells
• Humans
• Lipoproteins, LDL (chemistry)
• Liver (drug effects, metabolism, pathology)
• Liver Neoplasms (drug therapy, genetics, pathology)
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• RNA, Small Interfering (administration & dosage, genetics)