Barnase-Loaded Vaterite Nanoparticles Functionalized by EpCAM Targeting Vectors for the Treatment of Lung Diseases

Tatiana O. Abakumova, Olga I. Gusliakova, Julijana Cvjetinovic, Olga I. Efimova, Elena V. Konovalova, Alexey A. Schulga, Timofei S. Zatsepin, Dmitry A. Gorin, Alexey M. Yashchenok, Sergey M. Deyev

Research output: Contribution to journalArticlepeer-review

Abstract

Protein-based therapeutics is an emerging technology to combat various pathologies, including lung diseases. Particle-mediated delivery promotes its accumulation and increases therapeutic efficacy, minimizing side effects. Barnase (Bn) is a highly stable bacterial protein with ribonuclease (RNase) activity that affects cell proliferation. Encapsulation of Bn in particulate forms like liposomes or inorganic nanoparticles leads to its prolonged circulation in blood, but effective accumulation in targeted sites and subsequent internalization are still limited. In this work, we focus on the development of an effective delivery system with ribonuclease activity and specific accumulation in lung tissues. We fabricate multilayer Bn-loaded vaterite nanoparticles conjugated with targeting vector-aptamer specific to the epithelial cell adhesion molecule (EpCAM). Although two Bn layers in the particles do not result in an increase in loading efficiency, they do contribute significantly to ribonuclease activity (44.9 nM/min for (DS/Bn)2/DS vs 14.8 nM/min for DS/Bn/Ds) and enzyme stability (up to 90% of Bn activity for 7 days). We show that the conjugation of particles with EpCAM aptamer drastically increases particle internalization in human lung adenocarcinoma cells with a significant cytotoxic effect. In vivo biodistribution analysis reveals that intratracheal instillation of EpCAM-modified (DS/Bn)2/DS particles causes better accumulation of particles in lung tissues as identified by fluorescence imaging tomography and confocal microscopy. Thus, the developed targeted bilayer vaterite nanoparticles can be a promising protein-based delivery system for the treatment of lung diseases.

Original languageEnglish
Pages (from-to)10744-10754
Number of pages11
JournalACS Applied Nano Materials
Volume5
Issue number8
DOIs
Publication statusPublished - 26 Aug 2022

Keywords

  • activity
  • barnase
  • biodistribution
  • calcium carbonate
  • encapsulation
  • EpCAM
  • lung
  • toxicity

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