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Updated: Jul 20, 2026
Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
Published on: March 1, 2013
Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy
Adam C Midgley1,2, Yongzhen Wei3, Dashuai Zhu3
1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China midgleyac@nankai.edu.cn kongdeling@nankai.edu.cn.
Background:
Progressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype.
Methods:
We focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)-NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD.
Results:
Synthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which-following endocytosis driven by CD44+ cells-promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%-45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition.
Conclusions:
Nanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.
Insights
Nanoparticles delivering therapeutic genes like BMP7 or HGF/NK1 effectively inhibited fibrosis and improved kidney function in CKD mouse models. This offers a promising new strategy for treating chronic kidney disease.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Nanotechnology
Background:
- Progressive fibrosis is a key driver of chronic kidney disease (CKD).
- Targeting profibrotic cell phenotypes is crucial for developing effective CKD therapeutics.
- Nanoparticles offer novel delivery systems for antifibrotic therapies to damaged kidney tissues.
Purpose of the Study:
- To develop and evaluate hyaluronan-coated chitosan nanoparticles for delivering therapeutic genes to the kidneys.
- To assess the biocompatibility and antifibrotic efficacy of these nanoparticles both in vitro and in vivo.
- To investigate the potential of bone morphogenetic protein 7 (BMP7) and hepatocyte growth factor-NK1 (HGF/NK1) gene delivery for CKD treatment.
Main Methods:
- Chitosan nanoparticles were synthesized and coated with hyaluronan, encapsulating plasmid DNA encoding BMP7 or HGF/NK1.
- Nanoparticles were characterized for size and evaluated in vitro for biocompatibility and antifibrotic effects.
- Antifibrotic activity was assessed in vivo using unilateral ureteral obstruction mouse models of CKD, with noninvasive gene delivery via intravenous tail injection.
Main Results:
- Hyaluronan-coated nanoparticles demonstrated consistent size, promoted cellular growth, and inhibited fibrotic gene expression in vitro.
- In vivo studies showed approximately 40%-45% gene uptake in kidneys following intravenous administration.
- Nanoparticles attenuated fibrosis development and rescued renal function; BMP7 reversed fibrosis and regenerated tubules, while HGF/NK1 halted progression by reducing collagen deposition.
Conclusions:
- Nanoparticle-mediated delivery of HGF/NK1 demonstrated significant antifibrotic and proregenerative effects in CKD models.
- This research provides a proof-of-concept for enhanced targeting and transfection of therapeutic genes to kidney tissues.
- The study presents a promising avenue for the development of novel treatments for chronic kidney disease.
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