Engineering Lipid Nanoparticles to Enhance Intracellular Delivery of Transforming Growth Factor-Beta siRNA (siTGF-β1) via Inhalation for Improving Pulmonary Fibrosis Post-Bleomycin Challenge Article Swipe
Xu Deng
,
Yingjie Yang
,
Li‐Ming Gan
,
Xinliu Duan
,
Xiwei Wang
,
Jingyan Zhang
,
Aiping Wang
,
An-An Zhang
,
Zuyi Yuan
,
Daquan Chen
,
Aiping Zheng
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics17020157
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/pharmaceutics17020157
Background/Objectives: Transforming Growth Factor-beta (TGFβ1) plays a core role in the process of pulmonary fibrosis (PF). The progression of pulmonary fibrosis can be alleviated by siRNA-based inhibiting TGF-β1. However, the limitations of naked siRNA lead to the failure of achieving therapeutic effect. This study aimed to design lipid nanoparticles (LNPs) that can deliver siTGF-β1 to the lungs for therapeutic purposes. Methods: The cytotoxicity and transfection assay in vitro were used to screen ionizable lipids (ILs). Design of Experiments (DOE) was used to obtain novel LNPs that can enhance resistance to atomization shear forces. Meanwhile, the impact of LNPs encapsulating siTGF-β1 (siTGFβ1-LNPs) on PF was investigated. Results: When DLin-DMA-MC3 (MC3) was used as the ILs, the lipid phase ratio was MC3:DSPC:DMG-PEG2000:cholesterol = 50:10:3:37, and N/P = 3.25; the siTGFβ1-LNPs could be stably delivered to the lungs via converting the siTGFβ1-LNPs solution into an aerosol (atomization). In vitro experiments have confirmed that siTGFβ1-LNPs have high safety, high encapsulation, and can promote cellular uptake and endosomal escape. In addition, siTGFβ1-LNPs significantly reduced inflammatory infiltration and attenuated deposition of extracellular matrix (ECM) and protected the lung tissue from the toxicity of bleomycin (BLM) without causing systemic toxicity. Conclusions: The siTGFβ1-LNPs can be effectively delivered to the lungs, resulting in the silencing of TGF-β1 mRNA and the inhibition of the epithelial–mesenchymal transition pathway, thereby delaying the process of PF, which provides a new method for the treatment and intervention of PF.
Related Topics
Concepts
Bleomycin
Chemistry
Pulmonary fibrosis
Transforming growth factor
Fibrosis
Pulmonary toxicity
Extracellular matrix
Gene silencing
Transforming growth factor beta
Transfection
Lung
Cell biology
Cancer research
Toxicity
Medicine
Pathology
Biology
Biochemistry
Internal medicine
Chemotherapy
Gene
Organic chemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/pharmaceutics17020157
- OA Status
- gold
- Cited By
- 4
- References
- 34
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406782583
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4406782583Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/pharmaceutics17020157Digital Object Identifier
- Title
-
Engineering Lipid Nanoparticles to Enhance Intracellular Delivery of Transforming Growth Factor-Beta siRNA (siTGF-β1) via Inhalation for Improving Pulmonary Fibrosis Post-Bleomycin ChallengeWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-01-24Full publication date if available
- Authors
-
Xu Deng, Yingjie Yang, Li‐Ming Gan, Xinliu Duan, Xiwei Wang, Jingyan Zhang, Aiping Wang, An-An Zhang, Zuyi Yuan, Daquan Chen, Aiping ZhengList of authors in order
- Landing page
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https://doi.org/10.3390/pharmaceutics17020157Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.3390/pharmaceutics17020157Direct OA link when available
- Concepts
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Bleomycin, Chemistry, Pulmonary fibrosis, Transforming growth factor, Fibrosis, Pulmonary toxicity, Extracellular matrix, Gene silencing, Transforming growth factor beta, Transfection, Lung, Cell biology, Cancer research, Toxicity, Medicine, Pathology, Biology, Biochemistry, Internal medicine, Chemotherapy, Gene, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
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2025: 4Per-year citation counts (last 5 years)
- References (count)
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34Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 97 |
| corresponding_author_ids | https://openalex.org/A5055060757, https://openalex.org/A5022189674 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 11 |
| corresponding_institution_ids | https://openalex.org/I18452120 |
| citation_normalized_percentile.value | 0.97580173 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |