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Phosphocholine-Functionalized Zwitterionic Highly Branched Poly(β-amino ester)s for Cytoplasmic Protein Delivery
Yuhe Zhang1, Jiahao Shi1, Bin Ma1
1School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
ACS Macro Letters
|April 24, 2023
Summary
New zwitterionic polymers (HPAE-D-(±)) effectively deliver proteins into cells, overcoming biological barriers. This breakthrough offers a safer, more efficient method for protein-based therapies and vaccine development.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Proteins hold great promise for vaccines and disease treatment but face biological barriers to function.
- Effective protein delivery into cells, especially the cytoplasm, is hindered by challenges in packaging and cell penetration.
- Protein surface charges complicate delivery, necessitating advanced carrier systems.
Purpose of the Study:
- To develop a novel polymer system for efficient and safe cytoplasmic protein delivery.
- To investigate the role of zwitterionic functionalization in overcoming protein delivery challenges.
- To evaluate the efficacy and cytotoxicity of the developed protein delivery system.
Main Methods:
- Synthesis of phosphocholine-functionalized zwitterionic poly(β-amino ester)s (HPAE-D-(±)).
- Comparison with amine- (HPAE-E-(+)) and carboxylic acid-functionalized (HPAE-C-(-)) polymers.
- Assessment of protein packaging, cellular uptake, cytoplasmic delivery efficiency, and cytotoxicity.
Main Results:
- HPAE-D-(±) demonstrated superior cytoplasmic protein delivery efficiency compared to other tested polymers.
- The zwitterionic phosphocholine moiety facilitated protein binding and enhanced nanoparticle cellular uptake.
- HPAE-D-(±) exhibited significantly lower cytotoxicity and good degradability in aqueous solution.
Conclusions:
- Phosphocholine-functionalized zwitterionic poly(β-amino ester)s are effective carriers for cytoplasmic protein delivery.
- This zwitterionic strategy overcomes key barriers in protein delivery, offering improved safety and efficiency.
- The approach holds potential for broader applications in developing advanced protein-based therapeutics and vaccines.
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