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Recombinant High Density Lipoprotein Nanoparticles for Target-Specific Delivery of siRNA

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ABSTRACT

Purpose

Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for treatments of numerous diseases. However, the progress towards broad application of siRNA requires the development of safe and effective vectors that target to specific cells. In this study, we developed a novel recombinant high density lipoprotein (rHDL) vector with high siRNA encapsulation efficiency.

Methods

They were prepared by condensing siRNA with various commercial cationic polymers and coating the polyplex with a layer of lipids and apolipoprotein AI (apo AI). The rHDL nanoparticles were used to transfect SMMC-7721 hepatoma cells with stable luciferase expression. The uptake and intracellular trafficing of siRNA were also investigated.

Results

Characterization studies revealed these rHDL nanoparticles had similar physical properties as natural HDLs. The various rHDL formulations had high silencing efficiency (more than 70% knockdown) in hepatocytes with minimum cytotoxicity. Moreover, the uptake of rHDL by SMMC-7721 was confirmed to be mediated through the natural HDL uptake pathway.

Conclusions

The work described here demonstrated the optimized rHDL nanoparticles may offer a promising tool for siRNA delivery to the liver.

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Abbreviations

apo A-I:

apolipoprotein A-I

PEI:

polyethyleneimine

PLL:

poly-L-lysine

RES system:

reticuloendothelial system

rHDL:

recombinant high density lipoprotein

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was supported by grants from the Natural Science Foundation of China No. 30825045.

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Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China

    Mengjie Rui

  2. School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China

    Hailing Tang, Yan Li, Xiaohui Wei & Yuhong Xu

  3. National Key Laboratory of Oncogene & Related Genes, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China

    Yuhong Xu

Authors
  1. Mengjie Rui
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  2. Hailing Tang
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  3. Yan Li
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  4. Xiaohui Wei
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  5. Yuhong Xu
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Corresponding author

Correspondence to Yuhong Xu.

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Rui, M., Tang, H., Li, Y. et al. Recombinant High Density Lipoprotein Nanoparticles for Target-Specific Delivery of siRNA. Pharm Res 30, 1203–1214 (2013). https://doi.org/10.1007/s11095-012-0957-4

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  • DOI: https://doi.org/10.1007/s11095-012-0957-4

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