Reproducible and Characterized Method for Ponatinib Encapsulation into Biomimetic Lipid Nanoparticles as a Platform for Multi-Tyrosine Kinase-Targeted Therapy: ACS Applied Bio Materials

Assaf Zinger, Gherardo Baudo, Tomoyuki Naoi, Federica Giordano, Stefania Lenna, Matteo Massaro, April Ewing, Ha Ram Kim, Ennio Tasciotti, Jason T. Yustein, Francesca Taraballi

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Ponatinib (Pon) is a multi-tyrosine kinase inhibitor that demonstrated high efficiency for treating cancer. However, severe side effects caused by Pon off-targeting effects prevent its extensive use. Using our understanding into the mechanisms by which Pon is transported by bovine serum albumin in the blood, we have successfully encapsulated Pon into a biomimetic nanoparticle (NP). This lipid NP (i.e., "leukosomes") incorporates membrane proteins purified from activated leukocytes that enable immune evasion, and enhanced targeting of inflamed endothelium NPs have been characterized for their size, charge, and encapsulation efficiency. Membrane proteins enriched on the NP surface enabled modulation of Pon release. These NP formulations showed promising dose-response results on two different murine osteosarcoma cell lines, F420 and RF379. Our results indicate that our fabrication method is reproducible, nonuser-dependent, efficient in loading Pon, and applicable toward repurposing numerous therapeutic agents previously shelved due to toxicity profiles.

Original languageEnglish (US)
Pages (from-to)6737-6745
Number of pages9
JournalACS Appl. Bio Mater.
Volume3
Issue number10
DOIs
StatePublished - Oct 19 2020

Keywords

  • biomimicry
  • bovine serum albumin
  • liposomes
  • osteosarcoma
  • ponatinib

ASJC Scopus subject areas

  • Biomaterials
  • Chemistry(all)
  • Biomedical Engineering
  • Biochemistry, medical

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