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Related Experiment Videos

Sequence segregation improves non-covalent protein delivery.

Federica Sgolastra1, Coralie M Backlund1, E Ilker Ozay2

  • 1Department of Polymer Science & Engineering, University of Massachusetts, Amherst, MA 01003, United States.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 2, 2017
PubMed
Summary

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This summary is machine-generated.

Synthetic polymers effectively deliver large biomolecules into cells, overcoming plasma membrane barriers. Enhanced segregation in these polymers improves protein binding and cellular uptake for biomedical applications.

Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Polymer Chemistry

Background:

  • Plasma membrane impermeability hinders intracellular delivery of large biomolecules.
  • Protein transduction domains (PTDs) facilitate delivery but often require covalent fusion.
  • Need for efficient, versatile, non-covalent biological delivery vehicles.

Purpose of the Study:

  • Investigate the role of polymer sequence segregation on protein binding and cellular uptake.
  • Develop novel synthetic mimics inspired by PTDs for enhanced biomolecule delivery.
  • Evaluate the efficacy of these synthetic transporters for therapeutic protein delivery.

Main Methods:

  • Synthesized a series of polyoxanorbornene-based copolymers with varying hydrophobic/hydrophilic segregation (block, gradient, homopolymer).
Keywords:
Cell penetrating peptidesNon-covalent protein deliveryPep-1Protein bindingProtein transduction domain mimicsSequence segregation

Related Experiment Videos

  • Assessed protein binding and translocation efficiencies in Jurkat T cells and HEK293Ts.
  • Delivered Cre recombinase into a loxP-reporter T cell line to demonstrate functional gene recombination.

    • Main Results:

    • A strongly segregated block copolymer exhibited the highest protein binding and translocation efficiencies.
    • An intermediately segregated gradient copolymer also showed high efficacy, outperforming commercial agents.
    • Successful delivery and nuclear translocation of active Cre recombinase demonstrated the system's applicability.

    Conclusions:

    • Increasing segregation of hydrophobic and cationic moieties in polymeric mimics enhances non-covalent protein delivery.
    • These PTD-inspired polymers offer potent, versatile biological delivery agents.
    • Provides crucial design parameters for developing advanced research and biomedical delivery systems.