Cellular Internalization of Therapeutic Oligonucleotides by Peptide Amphiphile Nanofibers and Nanospheres

Creative Commons License

Mumcuoglu D., ŞARDAN EKİZ M., Gunay G., Tekinay T., TEKİNAY A. B., GÜLER M. Ö.

ACS APPLIED MATERIALS & INTERFACES, cilt.8, sa.18, ss.11280-11287, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 18
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1021/acsami.6b01526
  • Dergi Adı: ACS APPLIED MATERIALS & INTERFACES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.11280-11287
  • Anahtar Kelimeler: oligonucleotide delivery, peptide amphiphiles, glycoconjugates, self-assembly, internalization, glucose transporters, GLUCOSE TRANSPORTERS, GOLD NANOPARTICLES, DELIVERY, CANCER, DRUG, ANTISENSE, EXPRESSION, GENE, NANOSTRUCTURES, INHIBITION
  • Gazi Üniversitesi Adresli: Evet

Özet

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.