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MicroSPECT Imaging-Guided Treatment of Idiopathic Pulmonary Fibrosis in Mice with a Vimentin-Targeting 99mTc-Labeled N-Acetylglucosamine-Polyethyleneimine
- Source :
- Molecular Pharmaceutics. 18:4140-4147
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-β1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.
- Subjects :
- Pathology
medicine.medical_specialty
Small interfering RNA
medicine.drug_class
Pharmaceutical Science
Vimentin
macromolecular substances
Bleomycin
Immunostimulant
Idiopathic pulmonary fibrosis
chemistry.chemical_compound
Drug Discovery
Pulmonary fibrosis
medicine
Lung
biology
urogenital system
business.industry
Zymosan
technology, industry, and agriculture
respiratory system
medicine.disease
respiratory tract diseases
medicine.anatomical_structure
chemistry
biology.protein
Molecular Medicine
business
Subjects
Details
- ISSN :
- 15438392 and 15438384
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Molecular Pharmaceutics
- Accession number :
- edsair.doi...........04e8ec0e6146ffa4a5889dc205a7c80c