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Fine-tuning the pH trigger of self-assembly.

Arijit Ghosh1, Mark Haverick, Keith Stump

  • 1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.

Journal of the American Chemical Society
|February 8, 2012
PubMed
Summary

Researchers created smart peptide amphiphiles that self-assemble into nanofibers at tumor-like pH. This controllable self-assembly enhances drug delivery and medical imaging agent accumulation.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Chemical Biology

Background:

  • Smart materials can enhance drug delivery and imaging by responding to physiological cues.
  • Tumor microenvironments often exhibit slightly acidic extracellular pH.
  • Self-assembling peptide amphiphiles offer tunable properties for advanced applications.

Purpose of the Study:

  • To develop self-assembling peptide amphiphiles that transition morphology in response to pH changes.
  • To investigate the influence of imaging tags on self-assembly behavior.
  • To control the pH-triggered self-assembly for targeted delivery applications.

Main Methods:

  • Synthesized a series of peptide amphiphile molecules.
  • Utilized pH-dependent self-assembly studies in isotonic salt solutions.

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  • Characterized self-assembly morphology using phase diagrams and imaging tags.
  • Investigated the role of hydrophobic, hydrogen-bonding, electrostatic, and steric forces.

    • Main Results:

    • Peptide amphiphiles transformed from single molecules or micelles into nanofibers as pH decreased from 7.4 to 6.6.
    • The pH-triggered self-assembly was rapid, reversible, and concentration-dependent.
    • Incorporation of a Gd(DO3A) imaging tag shifted the transition to more acidic pH and induced micellar formation at high pH.
    • Systematic tuning of self-assembly morphology and transition pH was achieved by balancing intermolecular forces.

    Conclusions:

    • Developed pH-responsive peptide amphiphiles for smart material applications.
    • Demonstrated control over self-assembly morphology and transition pH through molecular design.
    • Showcased potential for enhanced accumulation of imaging or drug delivery agents in tumor microenvironments.