Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres

Didem Mumcuoglu, Melis Sardan Ekiz, Gokhan Gunay, Turgay Tekinay, Ayse B. Tekinay, Mustafa O. Guler

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19 Citations (Scopus)
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Abstract

Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.
Original languageEnglish
Pages (from-to)11280-11287
JournalACS Applied Materials & Interfaces
Volume8
Issue number18
DOIs
Publication statusPublished - 11 May 2016
Externally publishedYes

Keywords

  • oligonucleotide delivery
  • peptide amphiphiles
  • glycoconjugates
  • self-assembly
  • internalization
  • glucose transporters

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