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Zinc(II)-Cyclen Multifunctional Complex Module-Mediated Polycation-Based High-Performance pDNA Vectors
Zhaoming Chen1, Shuai Liu1, Weijie Liu1
1Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
ACS Biomaterials Science & Engineering
|November 30, 2021
Summary
Novel zinc(II)-coordinative cyclen modules enhance low molecular weight polyethylenimine (LMWPEI) for superior gene transfection. These modules improve DNA condensation, cellular uptake, and endosomal escape, leading to significantly higher transfection efficiency and cell viability.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- Gene delivery vectors are crucial for gene therapy.
- Polyethylenimine (PEI) is a common non-viral gene vector but has limitations.
- Enhancing PEI's efficiency and safety is an active research area.
Purpose of the Study:
- To develop novel multifunctional modules for modifying low molecular weight polyethylenimine (LMWPEI).
- To evaluate the performance of these modified vectors in gene transfection.
- To investigate the synergistic effects of the modules with PEI for overcoming gene delivery barriers.
Main Methods:
- Synthesis of zinc(II)-coordinative cyclen based multifunctional modules.
- Modification of LMWPEI with the developed modules.
- In vitro evaluation of DNA condensation, serum resistance, cellular uptake, and endosomal escape.
- Assessment of gene transfection efficiency and cell viability in various cell types.
Main Results:
- The novel modules significantly improved LMWPEI's gene transfection capabilities.
- A synergistic effect was observed between the functional module and PEI2.5k, enhancing barrier penetration.
- The optimal Zn-PCD mediated 160-fold higher luciferase activity compared to commercial PEI25k in ADSC stem cells.
- High cell viability (>90%) and excellent transfection efficiency were achieved in HepG2, 293T, and 293F cells.
Conclusions:
- Novel zinc(II)-coordinative cyclen modules effectively enhance LMWPEI as a DNA vector.
- The modified vectors demonstrate superior performance in gene transfection by addressing key biological barriers.
- This approach offers a promising strategy for developing high-performance, safe, and versatile non-viral gene delivery systems.
