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Related Experiment Video

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Surface Functionalized Polyhydroxyalkanoate Nanoparticles via SpyTag-SpyCatcher System for Targeted Breast Cancer

Jin Young Heo1, Min Kyung Sung1, Seonhye Jang1

  • 1Department of Nanoscience and Engineering, Inje University, Gimhae 50834, Republic of Korea.

Pharmaceutics
|June 27, 2025
PubMed
Summary

Polyhydroxyalkanoate (PHA) nanoparticles were surface-engineered using the SpyTag-SpyCatcher system for enhanced drug delivery. This modular approach enables targeted cellular uptake, improving nanomedicine applications.

Keywords:
AffibodyHER2SpyTag–SpyCatcherTATpolyhydroxyalkanoate

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Area of Science:

  • Biomaterials Science
  • Nanomedicine
  • Molecular Biology

Background:

  • Biodegradable polymers, particularly polyhydroxyalkanoates (PHAs), are promising for drug delivery due to their biocompatibility and sustainability.
  • Microbiome-derived PHAs offer a sustainable alternative for advanced therapeutic platforms.
  • Surface functionalization is key to enhancing the efficacy of nanoparticle-based drug delivery systems.

Purpose of the Study:

  • To engineer polyhydroxyalkanoate (PHA) nanoparticles (NPs) via the SpyTag-SpyCatcher system for improved cellular uptake.
  • To investigate the targeted delivery capabilities of PHA NPs functionalized with HER2-specific Affibody and/or TAT peptides.
  • To evaluate the impact of ligand composition on cellular internalization and therapeutic effects.

Main Methods:

  • Surface functionalization of PHA NPs using mEGFP-SpyTag for visualization.
  • Conjugation with HER2-specific Affibody-SpyCatcher and/or TAT-SpyCatcher peptides for targeted delivery.
  • Characterization of NP size (<200 nm) and surface charge, and assessment of cellular uptake and cytotoxicity in HER2-expressing cells.

Main Results:

  • Affibody-functionalized PHA NPs significantly increased internalization and cytotoxicity in HER2-overexpressing SK-BR-3 cells.
  • TAT-functionalized PHA NPs demonstrated broad cellular uptake across various cell types, independent of HER2 expression.
  • Dual-functionalized NPs showed varied effects based on HER2 expression, underscoring the importance of ligand selection for targeted delivery.

Conclusions:

  • SpyTag-SpyCatcher-mediated surface engineering provides a versatile and effective strategy for PHA NP functionalization.
  • This approach enables modular and robust active targeting for advanced nanomedicine applications.
  • The study highlights the potential of engineered PHA NPs for precise and efficient drug delivery.