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Molecular Parameter...
Molecular Parameters of siRNA-Cell Penetrating Peptide Nanocomplexes for Efficient Cellular Delivery
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van Asbeck, Alexander H. (författare)
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Beyerle, Andrea (författare)
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McNeill, Hesta (författare)
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Bovee-Geurts, Petra H. M. (författare)
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- Lindberg, Staffan (författare)
- Stockholms universitet,Institutionen för neurokemi
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Verdurmen, Wouter P. R. (författare)
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- Hällbrink, Mattias (författare)
- Stockholms universitet,Institutionen för neurokemi
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- Langel, Ülo (författare)
- Stockholms universitet,Institutionen för neurokemi
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Heidenreich, Olaf (författare)
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Brock, Roland (författare)
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(creator_code:org_t)
- 2013-04-30
- 2013
- Engelska.
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 7:5, s. 3797-3807
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 luctferase 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 olipnudeotide transfection agents.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- drug delivery
- siRNA therapeutics
- cell-penetrating peptides
- transfection
- electrostatic
- oligonucleotide nanoparticles
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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ACS Nano
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Till lärosätets databas
- Av författaren/redakt...
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van Asbeck, Alex ...
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Beyerle, Andrea
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McNeill, Hesta
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Bovee-Geurts, Pe ...
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Lindberg, Staffa ...
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Verdurmen, Woute ...
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visa fler...
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Hällbrink, Matti ...
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Langel, Ülo
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Heidenreich, Ola ...
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Brock, Roland
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Kemi
- Artiklar i publikationen
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ACS Nano
- Av lärosätet
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Stockholms universitet