Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells
Nanoscale drug delivery systems exhibit a broad range of applications and promising treatment possibilities for various medical conditions. Nanomedicine is of great interest, particularly for rare diseases still lacking a curative treatment such as cystic fibrosis (CF). CF is defined by a lack of Cl...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/4/553 |
| _version_ | 1797571414809640960 |
|---|---|
| author | A. Katharina Kolonko Nadine Bangel-Ruland Francisco M. Goycoolea Wolf-Michael Weber |
| author_facet | A. Katharina Kolonko Nadine Bangel-Ruland Francisco M. Goycoolea Wolf-Michael Weber |
| author_sort | A. Katharina Kolonko |
| collection | DOAJ |
| description | Nanoscale drug delivery systems exhibit a broad range of applications and promising treatment possibilities for various medical conditions. Nanomedicine is of great interest, particularly for rare diseases still lacking a curative treatment such as cystic fibrosis (CF). CF is defined by a lack of Cl<sup>−</sup> secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) and an increased Na<sup>+</sup> absorption mediated by the epithelial sodium channel (ENaC). The imbalanced ion and water transport leads to pathological changes in many organs, particularly in the lung. We developed a non-viral delivery system based on the natural aminopolysaccharide chitosan (CS) for the transport of antisense oligonucleotides (ASO) against ENaC to specifically address Na<sup>+</sup> hyperabsorption. CS–ASO electrostatic self-assembled nanocomplexes were formed at varying positive/negative (P/N) charge ratios and characterized for their physicochemical properties. Most promising nanocomplexes (P/N 90) displayed an average size of ~150 nm and a zeta potential of ~+30 mV. Successful uptake of the nanocomplexes by the human airway epithelial cell line NCI-H441 was confirmed by fluorescence microscopy. Functional Ussing chamber measurements of transfected NCI-H441 cells showed significantly decreased Na<sup>+</sup> currents, indicating successful downregulation of ENaC. The results obtained confirm the promising characteristics of CS as a non-viral and non-toxic delivery system and demonstrate the encouraging possibility to target ENaC with ASOs to treat abnormal ion transport in CF. |
| first_indexed | 2024-03-10T20:40:17Z |
| format | Article |
| id | doaj.art-a4e78e4308fc47a5884bb657e2bba731 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:40:17Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a4e78e4308fc47a5884bb657e2bba7312023-11-19T20:46:34ZengMDPI AGBiomolecules2218-273X2020-04-0110455310.3390/biom10040553Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial CellsA. Katharina Kolonko0Nadine Bangel-Ruland1Francisco M. Goycoolea2Wolf-Michael Weber3Institute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, GermanyInstitute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, GermanySchool of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UKInstitute of Animal Physiology, University of Muenster, Schlossplatz 8, 48143 Muenster, GermanyNanoscale drug delivery systems exhibit a broad range of applications and promising treatment possibilities for various medical conditions. Nanomedicine is of great interest, particularly for rare diseases still lacking a curative treatment such as cystic fibrosis (CF). CF is defined by a lack of Cl<sup>−</sup> secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) and an increased Na<sup>+</sup> absorption mediated by the epithelial sodium channel (ENaC). The imbalanced ion and water transport leads to pathological changes in many organs, particularly in the lung. We developed a non-viral delivery system based on the natural aminopolysaccharide chitosan (CS) for the transport of antisense oligonucleotides (ASO) against ENaC to specifically address Na<sup>+</sup> hyperabsorption. CS–ASO electrostatic self-assembled nanocomplexes were formed at varying positive/negative (P/N) charge ratios and characterized for their physicochemical properties. Most promising nanocomplexes (P/N 90) displayed an average size of ~150 nm and a zeta potential of ~+30 mV. Successful uptake of the nanocomplexes by the human airway epithelial cell line NCI-H441 was confirmed by fluorescence microscopy. Functional Ussing chamber measurements of transfected NCI-H441 cells showed significantly decreased Na<sup>+</sup> currents, indicating successful downregulation of ENaC. The results obtained confirm the promising characteristics of CS as a non-viral and non-toxic delivery system and demonstrate the encouraging possibility to target ENaC with ASOs to treat abnormal ion transport in CF.https://www.mdpi.com/2218-273X/10/4/553CFTRENaCchitosanantisense oligonucleotidesnanocomplexescystic fibrosis |
| spellingShingle | A. Katharina Kolonko Nadine Bangel-Ruland Francisco M. Goycoolea Wolf-Michael Weber Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells Biomolecules CFTR ENaC chitosan antisense oligonucleotides nanocomplexes cystic fibrosis |
| title | Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells |
| title_full | Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells |
| title_fullStr | Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells |
| title_full_unstemmed | Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells |
| title_short | Chitosan Nanocomplexes for the Delivery of ENaC Antisense Oligonucleotides to Airway Epithelial Cells |
| title_sort | chitosan nanocomplexes for the delivery of enac antisense oligonucleotides to airway epithelial cells |
| topic | CFTR ENaC chitosan antisense oligonucleotides nanocomplexes cystic fibrosis |
| url | https://www.mdpi.com/2218-273X/10/4/553 |
| work_keys_str_mv | AT akatharinakolonko chitosannanocomplexesforthedeliveryofenacantisenseoligonucleotidestoairwayepithelialcells AT nadinebangelruland chitosannanocomplexesforthedeliveryofenacantisenseoligonucleotidestoairwayepithelialcells AT franciscomgoycoolea chitosannanocomplexesforthedeliveryofenacantisenseoligonucleotidestoairwayepithelialcells AT wolfmichaelweber chitosannanocomplexesforthedeliveryofenacantisenseoligonucleotidestoairwayepithelialcells |