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pH-responsive zwitterionic copolypeptides as charge conversional shielding system for gene carriers
Huayu Tian1, Zhaopei Guo1, Lin Lin1
1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Summary
A novel shielding system, polyethylenimine-poly(l-lysine)-poly(l-glutamic acid) (PELG), enhances gene delivery. This pH-responsive polymer improves polyplex charge and tumor cell interaction for higher transfection efficiency.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Gene Delivery Systems
Background:
- Positively charged polyplexes face challenges in gene delivery due to non-specific interactions.
- pH-responsive materials offer potential for targeted delivery in tumor microenvironments.
Purpose of the Study:
- To design and evaluate a novel pH-responsive shielding system for polyplexes.
- To enhance the tumor-targeting ability and transfection efficiency of polyethylenimine (PEI)/DNA complexes.
Main Methods:
- Synthesis of a zwitterionic copolypeptide: polyethylenimine-poly(l-lysine)-poly(l-glutamic acid) (PELG).
- Formation of ternary polyplexes by shielding PEI25k/DNA with PELG.
- Characterization of polyplex surface zeta potential changes in response to pH variations.
Main Results:
- The PELG shielding system effectively coated positively charged PEI25k/DNA polyplexes.
- Ternary polyplexes exhibited a pH-responsive zeta potential, switching from negative to positive around pH 6.9.
- Restored positive charges at tumor extracellular pH (approx. 6.5) facilitated electrostatic interactions with negatively charged tumor cells.
Conclusions:
- The novel PELG shielding system demonstrates significant pH-responsive behavior.
- This system enhances polyplex interaction with tumor cells, leading to improved cell uptake and transfection efficiency.
- PELG holds promise as a component for advanced gene delivery vehicles targeting solid tumors.
