Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres
S. Ekiz, M.
Tekinay, A. B.
Guler, M. O.
ACS Applied Materials and Interfaces
American Chemical Society
11280 - 11287
Item Usage Stats
MetadataShow full item record
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.
Published Version (Please cite this version)https://doi.org/10.1021/acsami.6b01526
Showing items related by title, author, creator and subject.
Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG Yildiz, S.; Alpdundar, E.; Gungor, B.; Kahraman, T.; Bayyurt, B.; Gursel, I.; Gursel, M. (Wiley - V C H Verlag GmbH & Co. KGaA, 2015)Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized ...
Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels Uzunalli, G.; Tumtas, Y.; Delibasi, T.; Yasa, O.; Mercan, S.; Guler, M. O.; Tekinay, A. B. (Elsevier, 2015)Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel ...
Effect of egg storage duration and brooding temperatures on chick growth, intestine morphology and nutrient transporters Yalcin, S.; Gursel, I.; Bilgen, G.; Horuluoglu, B. H.; Gucluer, G.; Izzetoglu, G. T. (Cambridge University Press, 2017-10)The effects of egg storage duration (ESD) and brooding temperature (BT) on BW, intestine development and nutrient transporters of broiler chicks were investigated. A total of 396 chicks obtained from eggs stored at 18°C ...