Browsing by Subject "Cellular internalization"

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    Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres
    (American Chemical Society, 2016-04) Mumcuoglu, D.; S. Ekiz, M.; Gunay, G.; Tekinay, T.; Tekinay, A. B.; Güler, Mustafa O.
    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.
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    Nanosized delivery systems for tissue regeneration
    (John Wiley & Sons, 2016-03-11) Çınar, Göksu; Mumcuoğlu, Didem; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.
    This chapter focuses on advanced delivery of biologics including growth factors (GFs), cytokines, genes, or siRNAs using a variety of nanosized systems for different regeneration applications focusing on bone, cartilage, nervous system, and muscle regeneration strategies. Gene therapy provides permanent genetic alteration, but only transient actions of protein therapeutics can be needed for tissue regeneration applications. The limitations of biologics delivery and alternative strategies for overcoming recent problems are underlined presenting recent examples from the literature. In addition, specific targeting and cellular internalization strategies of biologies delivery for tissue regeneration are discussed for providing future perspectives to the readers in this field. Overall, it is believed that advanced nanosized delivery systems integrated with multicomponent designs will open new opportunities in delivery technologies and strategies for tissue regeneration.