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Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib

Kateřina Jáklová1, Tereza Feglarová1, Simona Rex2,3

  • 1Department of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech Republic.

International Journal of Molecular Sciences
|April 30, 2021
PubMed

Insights

Apoferritin-bound vandetanib (ApoVan) was developed to reduce anticancer drug cardiotoxicity. While stable and releasing vandetanib, ApoVan showed similar toxicity to free vandetanib, suggesting surface binding rather than encapsulation.

Area of Science:

  • Nanotechnology
  • Pharmacology
  • Oncology

Background:

  • Vandetanib (Van) is an anticancer drug targeting VEGFR, EGFR, and RET protooncogenes.
  • Its use in medullary thyroid cancer is limited by cardiotoxicity.
  • Nanocarrier-based drug delivery aims to improve targeted delivery and reduce side effects.

Purpose of the Study:

  • To construct and characterize a novel nanocarrier, apoferritin associated with vandetanib (ApoVan).
  • To evaluate the stability, drug release profile, and in vitro cytotoxicity of ApoVan.
  • To investigate the potential of apoferritin as a carrier for vandetanib to mitigate side effects.

Main Methods:

  • Synthesis and characterization of ApoVan nanoparticles (size, ζ-potential, polydispersity index).
  • Assessment of ApoVan stability during storage.
  • In vitro drug release studies at neutral (pH 7.4) and acidic (pH 6.5) conditions.
  • Cytotoxicity assays of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines.

Main Results:

  • ApoVan nanoparticles demonstrated long-term stability and maintained morphology.
  • The ApoVan complex was stable during storage and exhibited gradual release of Van in both neutral and acidic environments.
  • Both free Van and ApoVan displayed comparable toxicity against the tested cancer cell lines.

Conclusions:

  • Apoferritin-based nanocarriers are stable and capable of releasing vandetanib.
  • The observed similar toxicity suggests that vandetanib may bind to the surface of apoferritin rather than being encapsulated within its cavity.
  • Further research is needed to optimize encapsulation for targeted delivery and reduced cardiotoxicity.
Keywords:
apoferritincancer targetingmedullary thyroid cancerneuroblastomavandetanib

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