Preclinical study of biofunctional polymer-coated upconversion nanoparticles

Evgenii L. Guryev, Natalia Y. Shilyagina, Alexey B. Kostyuk, Ludmila M. Sencha, Irina V. Balalaeva, Vladimir A. Vodeneev, Olga M. Kutova, Alexander V. Lyubeshkin, Raisa I. Yakubovskaya, Andrei A. Pankratov, Faina I. Ingel, Tamara S. Novik, Sergey M. Deyev, Sergey A. Ermilov, Andrei V. Zvyagin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9-29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.

Original languageEnglish
Pages (from-to)123-132
Number of pages10
JournalToxicological Sciences
Volume170
Issue number1
DOIs
Publication statusPublished - 1 Jul 2019

Keywords

  • Animal imaging
  • Nanotoxicology
  • Pharmacodynamics
  • Pharmacokinetics
  • Photoluminescent nanomaterials
  • Upconversion nanoparticles

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