Enhanced Gene Silencing through Human Serum Albumin-Mediated Delivery of Polyethylenimine-siRNA Polyplexes
| Autor: | V. Prasad Shastri, Michela Bosetti, Elena Nicolì, Marie Isabel Syga |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Small interfering RNA
Macromolecular Substances media_common.quotation_subject Serum albumin lcsh:Medicine Electrophoretic Mobility Shift Assay Caveolae chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor medicine Humans Polyethyleneimine Gene silencing Gene Silencing RNA Small Interfering lcsh:Science Internalization Serum Albumin media_common Polyethylenimine Multidisciplinary biology lcsh:R Endothelial Cells Transfection Flow Cytometry Human serum albumin Molecular biology Blood proteins Cell biology chemistry biology.protein lcsh:Q Research Article medicine.drug |
| Zdroj: | PLoS ONE, Vol 10, Iss 4, p e0122581 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0122581 |
| Popis: | Small interfering RNA (siRNA) targeted therapeutics (STT) offers a compelling alternative to tradition medications for treatment of genetic diseases by providing a means to silence the expression of specific aberrant proteins, through interference at the expression level. The perceived advantage of siRNA therapy is its ability to target, through synthetic antisense oligonucleotides, any part of the genome. Although STT provides a high level of specificity, it is also hindered by poor intracellular uptake, limited blood stability, high degradability and non-specific immune stimulation. Since serum proteins has been considered as useful vehicles for targeting tumors, in this study we investigated the effect of incorporation of human serum albumin (HSA) in branched polyethylenimine (bPEI)-siRNA polyplexes in their internalization in epithelial and endothelial cells. We observed that introduction of HSA preserves the capacity of bPEI to complex with siRNA and protect it against extracellular endonucleases, while affording significantly improved internalization and silencing efficiency, compared to bPEI-siRNA polyplexes in endothelial and metastatic breast cancer epithelial cells. Furthermore, the uptake of the HSA-bPEI-siRNA ternary polyplexes occurred primarily through a caveolae-mediated endocytosis, thus providing evidence for a clear role for HSA in polyplex internalization. These results provide further impetus to explore the role of serum proteins in delivery of siRNA. |
| Databáze: | OpenAIRE |
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