AI Article Synopsis
- The CD44 protein is a key receptor on tumor cells that binds hyaluronan (HA), but the weak interaction limits effective drug delivery.
- Researchers enhanced HA's binding to CD44 using a HA tetrasaccharide cluster and modified a polyamidoamine (PAMAM) dendrimer for better siRNA delivery.
- The resulting nanocomplexes improved siRNA uptake in cells, successfully reducing GFP protein and mRNA levels, which could enhance the use of PAMAM nanomaterials in clinical settings.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027316 | PMC |
| http://dx.doi.org/10.3390/nano8060433 | DOI Listing |
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