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Anti-Inflammatory Effect of Anti-TNF-α SiRNA Cationic Phosphorus Dendrimer Nanocomplexes Administered Intranasally in a Murine Acute Lung Injury Model
- Source :
- Biomacromolecules, Biomacromolecules, American Chemical Society, 2017, 18 (8), pp.2379-2388. ⟨10.1021/acs.biomac.7b00572⟩, Biomacromolecules, 2017, 18 (8), pp.2379-2388. ⟨10.1021/acs.biomac.7b00572⟩
- Publication Year :
- 2017
- Publisher :
- American Chemical Society (ACS), 2017.
-
Abstract
- International audience; Inflammation is an essential component of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), or acute lung injury. Our purpose was to design efficient carriers for lung delivery of small interfering RNA (siRNA) targeting tumor necrosis factor (TNF-α) in an acute lung injury model. To achieve this goal, two different types of phosphorus-based dendrimers with either pyrrolidinium or morpholinium as terminal protonated amino groups were selected for their better biocompatibility compared to other dendrimers. Dendriplexes containing pyrrolidinium surface groups demonstrated a stronger siRNA complexation, a higher cellular uptake, and enhanced in vitro silencing efficiency of TNF-α in the lipopolysaccharide (LPS)-activated mouse macrophage cell line RAW264.7, compared to morpholinium-containing dendriplexes. The better performance of the pyrrolidium dendriplexes was attributed to their higher pKa value leading to a stronger siRNA complexation and improved protection against enzymatic degradation resulting in a higher cellular uptake. The superior silencing effect of the pyrrolidinium dendriplexes, compared to noncomplexed siRNA, was confirmed in vivo in an LPS-induced murine model of short-term acute lung injury upon lung delivery via nasal administration. These data suggest that phosphorus dendriplexes have a strong potential in lung delivery of siRNA for treating inflammatory lung diseases.
- Subjects :
- 0301 basic medicine
Dendrimers
Small interfering RNA
Polymers and Plastics
Lipopolysaccharide
Acute Lung Injury
Anti-Inflammatory Agents
Bioengineering
Inflammation
02 engineering and technology
Lung injury
Pharmacology
Small Interfering
Morpholinos
Biomaterials
Mice
03 medical and health sciences
chemistry.chemical_compound
Materials Chemistry
medicine
Animals
Gene silencing
[CHIM.COOR]Chemical Sciences/Coordination chemistry
Gene Silencing
RNA, Small Interfering
Administration, Intranasal
Disease Models, Animal
Female
RAW 264.7 Cells
Tumor Necrosis Factor-alpha
Animal
Chemistry
021001 nanoscience & nanotechnology
In vitro
3. Good health
030104 developmental biology
Intranasal
Administration
Disease Models
Immunology
RNA
Nasal administration
Tumor necrosis factor alpha
medicine.symptom
0210 nano-technology
Subjects
Details
- ISSN :
- 15264602 and 15257797
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Biomacromolecules
- Accession number :
- edsair.doi.dedup.....4118e78876cfa00089b692e7870bcba3