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Functionalised thermally induced phase separation (TIPS) microparticles enabled for "click" chemistry.

João C F Nogueira1, Ketevan Paliashvili2, Alexandra Bradford2

  • 1UCL Chemistry Department, University College London, Gower Street, London, WC1E 6BT, UK. v.chudasama@ucl.ac.uk.

Organic & Biomolecular Chemistry
|March 10, 2020
PubMed
Summary

Thermally induced phase separation (TIPS) microparticles were functionalized with Herceptin Fab fragments using a novel click chemistry linker. This method enhanced binding avidity to HER2+ targets compared to traditional antibody physisorption.

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Nanotechnology

Background:

  • Thermally induced phase separation (TIPS) microparticles offer advantages like homogeneity, tuneable properties, low cost, and ease of manufacture for tissue repair and disease treatment.
  • Current limitations exist in enhancing the surface functionalization of TIPS microparticles for targeted therapies.

Purpose of the Study:

  • To develop and evaluate an improved method for surface functionalization of TIPS microparticles.
  • To compare the efficacy of a novel click chemistry-based functionalization approach with traditional antibody physisorption for targeted delivery.

Main Methods:

  • Functionalization of TIPS microparticles with small molecules and an antibody fragment (Herceptin Fab) using a pyridazinedione linker.
  • Utilizing SPAAC (Scopper-free click chemistry) for efficient conjugation.
  • Comparison of antigen-binding avidity with microparticles prepared via traditional antibody physisorption.

Main Results:

  • Successful functionalization of TIPS microparticles with Herceptin Fab via the pyridazinedione linker and click chemistry.
  • Demonstrated enhanced avidity of functionalized microparticles to HER2+ targets compared to physisorption methods.
  • The novel linker approach provides superior targeted binding capabilities.

Conclusions:

  • The pyridazinedione linker and SPAAC click chemistry offer a superior method for functionalizing TIPS microparticles for targeted applications.
  • This enhanced functionalization strategy improves the avidity of microparticles for specific targets, such as HER2+.
  • This approach holds promise for advanced injectable devices in tissue engineering and cancer therapy.