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Open AccessArticle

Construction of Hyaluronic Tetrasaccharide Clusters Modified Polyamidoamine siRNA Delivery System

by Yingcong Ma 1,†, Meng Sha 2,†, Shixuan Cheng 1,†, Wang Yao 2, Zhongjun Li 2,* and Xian-Rong Qi 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
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nanomaterials 2018, 8(6), 433; https://doi.org/10.3390/nano8060433
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)
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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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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