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A Multilayer Microfluidic Platform for the Conduction of Prolonged Cell-Free Gene Expression
Published on: October 6, 2019
10.7K
Multiply clustered gold-based nanoparticles complexed with exogenous pDNA achieve prolonged gene expression in stem
Se Won Yi1, Ji Sun Park1, Hye Jin Kim1
1Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Biocomplex, Sampyeong-Dong, Bundang-gu, Seongnam-si, 13488, Republic of Korea.
Theranostics
|August 15, 2019
Summary
We developed multiply-clustered gold-based nanoparticles (mCGNPs) for stable gene delivery in stem cells. This system enhances chondrogenic differentiation by prolonging SOX9 expression, improving gene therapy outcomes.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Stem Cell Biology
Background:
- Developing stable and prolonged gene delivery systems is crucial for advancing gene therapy.
- Current gene delivery methods often lack efficiency and longevity in stem cells.
- Controlled differentiation of stem cells holds therapeutic potential but requires effective gene modulation.
Purpose of the Study:
- To design and fabricate a novel gene delivery system using multiply-clustered gold nanoparticles (mCGNPs).
- To evaluate the efficiency, cytotoxicity, and gene expression duration of mCGNPs in human mesenchymal stem cells (hMSCs).
- To assess the application of mCGNPs for inducing chondrogenic differentiation in hMSCs via SOX9 gene delivery.
Main Methods:
- Fabrication of mCGNPs through sequential complexation of gold nanoparticles (AuNPs) with catechol-functionalized polyethyleneimine (CPEI), plasmid DNAs (pDNAs), and heparin (HP).
- Utilized metal-catechol interactions for AuNP surface coordination with CPEI and subsequent pDNA binding.
- Transfection of hMSCs with mCGNPs carrying SOX9 pDNA and evaluation of chondrogenic differentiation markers.
Main Results:
- mCGNPs demonstrated improved transfection efficiency, reduced cytotoxicity, and prolonged pDNA expression in hMSCs compared to conventional nanoparticles.
- Heparin encapsulation via electrostatic interactions contributed to NP compactness and stability.
- Prolonged SOX9 expression induced by mCGNPs successfully triggered chondrocyte extracellular matrix protein expression, leading to efficient chondrogenic differentiation both in vitro and in vivo.
Conclusions:
- Multiply-clustered gold-based nanoparticles represent a promising platform for stable and prolonged gene delivery in stem cells.
- This novel gene delivery system effectively promotes chondrogenic differentiation of hMSCs.
- The mCGNP system offers a viable strategy for enhancing gene therapy applications, particularly in regenerative medicine.
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