Event Abstract

Surface charge tunability as a powerful strategy to control electrostatic interaction for highly efficient delivery of nucleic acids, using tailored oligopeptide-modified poly(beta-amino ester)s (PBAEs)

  • 1 Institut Químic de Sarrià, Universitat Ramon Llull, Grup d’Enginyera de Materials (GEMAT), Spain

Introduction

The clinical development of synthetic vectors for gene therapy is still far from optimal[1]. Since synthetic vectors are mainly held together electrostatically and typically present high positively charged surfaces, the nature and the extent of their surface charge condition not only their interaction with the cell surface but also with other charged surfaces. Indeed, vector interactions with elements found in the extracellular matrix or the cell surface may interfere their interactions with target cells, resulting in decreased delivery efficiency[2]. Here, we present the use of mixtures of cationic and anionic oligopeptide-modified poly(beta-amino ester) (pBAE) polymers to tailor the surface charge of the resulting nanoparticles, while maintaining their ability to mediate efficient transfection.

Materials and Methods

pBAE polymers with cationic and anionic oligopeptide-modified termini were synthesized[3]. Biophysical characterization and in vitro performance of the resulting vectors was performed in the absence and presence of relevant biological media. 

Results and Discussion

Accurate formulation of positively- and negatively-charged pBAE polymers allowed control of nanoparticle composition and features, especially zeta potential, which could be fine-tuned depending on the amino acid nature of pBAE polymers. Analysis of the chemical composition of the nanoparticles revealed that the ratio of cationic and anionic pBAE polymers was maintained upon complexation. Therefore, these results suggest that the difference in zeta potential may necessarily derive from the different packing distribution of nucleic acids with cationic and anionic pBAE polymers.

Formulations of cationic and anionic pBAE polymers were evaluated in vitro by either transfecting cells using plasmid encoding for the green fluorescent protein (pGFP) or by silencing green fluorescent protein in GFP-expressing cells using anti-GFP siRNA. Analysis of cell fluorescence revealed that formulations of pBAE polymers were more efficient than single pBAE polymers and commercial controls. Despite showing better efficiency, mixtures of pBAE polymers resulted in lower cellular uptake, suggesting that probably endosomal escape or unpacking features were more efficient than in particles prepared from single pBAE polymers.

Conclusion

We have here demonstrated that appropriate formulation of delivery vectors using cationic and anionic pBAE polymers is a powerful approach to control their biophysical properties in order to reduce interfering interactions with the biological milieu, while maintaining their high delivery efficiency. This strategy has potential to overcome current in vivo limitations of synthetic vectors and may expand their scope of use beyond in vitro applications. 

References:
[1] D. Haussecker, J Control Release, 195, 49-54 (2014)
[2] L. Novo, J Control Release, 195, 162-175 (2014)
[3] P. Dosta, Acta Biomaterialia, 20, 82-93 (2015)

Keywords: nanoparticle, gene delivery, Non-viral vector, Polymeric material

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Biomaterials in gene therapy

Citation: Dosta P, Segovia N, Ramos V and Borros S (2016). Surface charge tunability as a powerful strategy to control electrostatic interaction for highly efficient delivery of nucleic acids, using tailored oligopeptide-modified poly(beta-amino ester)s (PBAEs). Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00716

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Received: 27 Mar 2016; Published Online: 30 Mar 2016.