Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer

Evgenii L. Guryev, Natalia O. Volodina, Natalia Y. Shilyagina, Sergey V. Gudkov, Irina V. Balalaeva, Arthur B. Volovetskiy, Alexander V. Lyubeshkin, Alexey V. Sen, Sergey A. Ermilov, Vladimir A. Vodeneev, Rem V. Petrov, Andrei V. Zvyagin*, Zhores I. Alferov, Sergey M. Deyev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90Y- and PE40-induced cytotoxic effects characterized by IC50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.

Original languageEnglish
Pages (from-to)9690-9695
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number39
DOIs
Publication statusPublished - 25 Sep 2018

Keywords

  • Combined therapy
  • Nuclear medicine
  • Targeted therapy
  • Theranostics
  • Upconversion nanoparticles

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