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Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles

Sigg, Severin J. and Postupalenko, Viktoriia and Duskey, Jason T. and Palivan, Cornelia G. and Meier, Wolfgang . (2016) Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles. Biomacromolecules, 17 (3). pp. 935-945.

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Official URL: http://edoc.unibas.ch/44228/

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Abstract

Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d-leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli-responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100–200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects.
Faculties and Departments:05 Faculty of Science > Departement Chemie
05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
UniBasel Contributors:Meier, Wolfgang P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:1525-7797
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 Sep 2016 13:53
Deposited On:28 Sep 2016 13:53

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