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Nanomaterials 2018, 8(6), 433; https://doi.org/10.3390/nano8060433

Construction of Hyaluronic Tetrasaccharide Clusters Modified Polyamidoamine siRNA Delivery System

1,†
,
2,†
,
1,†
,
2
,
2,* and 1,*
1
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2
State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 11 May 2018 / Revised: 1 June 2018 / Accepted: 5 June 2018 / Published: 14 June 2018
(This article belongs to the Special Issue Pharmaceutical Nanotechnology)
View Full-Text   |   Download PDF [1970 KB, uploaded 14 June 2018]   |  

Abstract

The CD44 protein, as a predominant receptor for hyaluronan (HA), is highly expressed on the surface of multiple tumor cells. HA, as a targeting molecule for a CD44-contained delivery system, increases intracellular drug concentration in tumor tissue. However, due to the weak binding ability of hyaluronan oligosaccharide to CD44, targeting for tumor drug delivery has been restricted. In this study, we first use a HA tetrasaccharide cluster as the target ligand to enhance the binding ability to CD44. A polyamidoamine (PAMAM) dendrimer was modified by a HA tetrasaccharide cluster as a nonviral vector for small interfering RNA (siRNA) delivery. The dendrimer/siRNA nanocomplexes increased the cellular uptake capacity of siRNA through the CD44 receptor-mediated endocytosis pathway, allowing the siRNA to successfully escape the endosome/lysosome. Compared with the control group, nanocomplexes effectively reduced the expression of GFP protein and mRNA in MDA-MB-231-GFP cells. This delivery system provides a foundation to increase the clinical applications of PAMAM nanomaterials. View Full-Text
Keywords: hyaluronic acid tetrasaccharide; CD44 protein; polyamidoamine (PAMAM) dendrimer; small interfering RNA; cellular uptake; endosome escape hyaluronic acid tetrasaccharide; CD44 protein; polyamidoamine (PAMAM) dendrimer; small interfering RNA; cellular uptake; endosome escape
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ma, Y.; Sha, M.; Cheng, S.; Yao, W.; Li, Z.; Qi, X.-R. Construction of Hyaluronic Tetrasaccharide Clusters Modified Polyamidoamine siRNA Delivery System. Nanomaterials 2018, 8, 433.

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