Oligonucleotide Delivery with Cell Surface Binding and Cell Penetrating Peptide Amphiphile Nanospheres

Autor: Mustafa O. Guler, Turgay Tekinay, Melis Sardan, Ayse B. Tekinay, Didem Mumcuoglu
Přispěvatelé: Mumcuoğlu, Didem, Sardan, Melis, Güler, Mustafa O., Tekinay, Ayşe. B.
Jazyk: angličtina
Rok vydání: 2015
Předmět:
carrier proteins and binding proteins
polyarginine
receptor binding
Pharmaceutical Science
Peptide
arginine
Cell-Penetrating Peptides
amphophile
incubation time
Drug Discovery
drug delivery system
Internalization
comparative study
media_common
mass spectrometry
chemistry.chemical_classification
pinocytosis
Microscopy
Confocal
oblimersen
Chemistry
Circular Dichroism
Transfection
particle size
Flow Cytometry
unclassified drug
cell surface
Biochemistry
priority journal
Drug delivery
MCF-7 Cells
Molecular Medicine
cytotoxicity
cellular internalization
Nanospheres
in vitro study
Cell Survival
media_common.quotation_subject
cell penetrating peptides
oligonucleotide delivery
Article
zeta potential
biocompatibility
Microscopy
Electron
Transmission
complex formation
Amphiphile
parasitic diseases
peptide synthesis
transmission electron microscopy
Peptide amphiphile
endocytosis
liquid chromatography
Humans
controlled study
cell surface proteoglycan binding peptide
Oligonucleotide
flow cytometry
static electricity
Oligonucleotides
Antisense
cell surface binding peptide
nanosphere
amino acid sequence
circular dichroism
solid phase synthesis
internalization
g 3129
cell penetrating peptide
MCF 7 cell line
hydrodynamics
Biophysics
Cell-penetrating peptide
gene expression
genetic transfection
protein secondary structure
cell membrane
Zdroj: Molecular Pharmaceutics
Molecular Pharmeceutics
Popis: A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonucleotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonucleotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R4 and R8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R8-PA and KRSR-PA. R8 and R8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs. © 2015 American Chemical Society.
Databáze: OpenAIRE
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