Academic Journal
Molecular Parameters of siRNA-Cell Penetrating Peptide Nanocomplexes for Efficient Cellular Delivery
| العنوان: | Molecular Parameters of siRNA-Cell Penetrating Peptide Nanocomplexes for Efficient Cellular Delivery |
|---|---|
| المؤلفون: | Asbeck, A.H. van, Beyerle, A., McNeill, H., Bovee-Geurts, P.H.M., Lindberg, S., Verdurmen, W.P.R., Hallbrink, M., Langel, U., Heidenreich, O., Brock, R.E. |
| المصدر: | ACS Nano, 7, 5, pp. 3797-807 |
| سنة النشر: | 2013 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | NCMLS 7: Chemical and physical biology |
| الوصف: | Item does not contain fulltext ; Cell-penetrating peptides (CPPs) are versatile tools for the intracellular delivery of various biomolecules, including siRNA. Recently, CPPs were introduced that showed greatly enhanced delivery efficiency. However, the molecular basis of this increased activity is poorly understood. Here, we performed a detailed analysis of the molecular and physicochemical properties of seven different siRNA-CPP nanoparticles. In addition, we determined which complexes are internalized most efficiently into the leukemia cell-line SKNO-1, and subsequently inhibited the expression of a luciferase reporter gene. We demonstrated effective complexation of siRNA for all tested CPPs, and optimal encapsulation of the siRNA was achieved at very similar molar ratios independent of peptide charge. However, CPPs with an extreme high or low overall charge proved to be exceptions, suggesting an optimal range of charge for CPP-siRNA nanoparticle formation based on opposite charge. The most active CPP (PepFect6) displayed high serum resistance but also high sensitivity to decomplexation by polyanionic macromolecules, indicating the necessity for partial decomplexation for efficient uptake. Surprisingly, CPP-siRNA complexes acquired a negative zeta-potential in the presence of serum. These novel insights shed light on the observation that cell association is necessary but not sufficient for activity and motivate new research into the nature of the nanoparticle-cell interaction. Overall, our results provide a comprehensive molecular basis for the further development of peptide-based oligonucleotide transfection agents. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | http://hdl.handle.net/2066/118811 |
| DOI: | 10.1021/nn305754c |
| الاتاحة: | http://hdl.handle.net/2066/118811 https://doi.org/10.1021/nn305754c |
| رقم الانضمام: | edsbas.B68C205C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/nn305754c |
|---|