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February 2, 2017Langmuir

A Zwitterionic-Shielded Carrier with pH-Modulated Reversible Self-Assembly for Gene Transfection

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Authors

YSYu‐Ju ShihAVAntoine VenaultLTLemmuel L. Tayo

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Overview

In vitro evaluation demonstrates improved hemocompatibility and acid-triggered transfection of zwitterionic core-shell polyplexes, indicating potential for safe, pH-responsive gene delivery.

Key Points

  • To develop and evaluate a pH-sensitive, zwitterionic-shielded core-shell polyplex system that overcomes the high cytotoxicity of cationic gene delivery vectors while maintaining high transfection efficiency.
  • Engineered core-shell polyplexes containing cationic cores of PEI or PDMAEMA complexed with DNA, enveloped by a zwitterionic PAA-b-PSBMA diblock copolymer shell.
  • Verified polymer-DNA complexation using gel retardation and ethidium bromide displacement assays.
  • Evaluated hemocompatibility via hemolysis and plasma clotting time assays, and assessed transfection efficiency at pH 6.5 versus pH 7.0 using β-galactosidase reporter assays alongside zeta potential and particle size characterization.
  • The zwitterionic PAA-b-PSBMA shell reduced cytotoxicity and improved hemocompatibility, producing lower hemolysis activity and extended plasma clotting times at neutral pH.
  • Deshielding of the copolymer shell in acidic conditions enabled higher gene transfection efficiency at pH 6.5 compared to pH 7.0 across all tested formulations, supported by acid-favorable zeta potential and particle size profiles.

Cite This Study

Shih et al. (2017) studied this question.

synapsesocial.com/papers/6a9e3d429b2dbee2f936855dhttps://doi.org/10.1021/acs.langmuir.6b03685
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