Computational Study of Drug Delivery Systems with Radionuclide and Fluorescence Imaging Modalities. I. Albumin-Based Systems for Doxorubicin Delivery

  • V. Trusova Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-7087-071X
  • U. Tarabara Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-7677-0779
  • I. Karnaukhov v National Science Center “Kharkov Institute of Physics and Technology”, Kharkiv, Ukraine
  • A. Zelinsky National Science Center “Kharkov Institute of Physics and Technology”, Kharkiv, Ukraine https://orcid.org/0000-0002-4110-8523
  • B. Borts National Science Center “Kharkov Institute of Physics and Technology”, Kharkiv, Ukraine https://orcid.org/0000-0002-1492-4066
  • I. Ushakov National Science Center “Kharkov Institute of Physics and Technology”, Kharkiv, Ukraine
  • L. Sidenko National Science Center “Kharkov Institute of Physics and Technology”, Kharkiv, Ukraine
  • G. Gorbenko Department of Medical Physics and Biomedical Nanotechnologies, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-0954-5053
DOI: https://doi.org/10.26565/2312-4334-2024-4-54
Keywords: Drug delivery systems, Human serum albumin, Doxorubicin, Technetium complexes, Fluorescent dyes, Molecular docking, Molecular dynamics

Abstract

Molecular docking and molecular dynamics methodologies were employed to design and evaluate delivery systems for the antineoplastic agent doxorubicin (DOX) utilizing human serum albumin (HSA) as the carrier. To engineer a drug delivery system (DDS) with dual imaging modalities, complexes of the radionuclide technetium-99m (TCC) and near-infrared (NIR) fluorescent dyes, including indocyanine green (IG), methylene blue (MB), heptamethine cyanine dye AK7-5, and squaraine dye SQ1, were integrated into the protein nanocarriers. The highest binding affinities to the proteins were identified for TCC [99mTc]Tc-diisopropyl iminodiacetic acid (TcDIS), [99mTc]Tc-hydrazinonicotinic acid-H6F (TcHYN), [99mTc]Tc-Mebrofenin (TcMEB), as well as the fluorescent dyes IG and SQ1. Molecular docking analyses revealed that most technetium complexes (TCCs) bind to HSA domain I, with some exceptions showing affinity for domains I and III or domain III alone. Ternary and quaternary protein-ligand systems were explored using multiple ligand docking approaches. In ternary systems, DOX binding sites were identified either in domain I or in a region spanning multiple domains, depending on potential overlap with TCC binding sites. For quaternary systems incorporating NIR fluorophores, binding affinities decreased in the order: IG > SQ1 > AK7-5 > MB. Molecular dynamics simulations of HSA-DOX-MB and HSA-DOX-IG complexes demonstrated stable associations between the components, with consistent center-of-mass distances and minimal perturbation of HSA structure. These findings support the potential of HSA as a suitable carrier for developing dual-modality imaging nanocarriers incorporating both radionuclide and fluorescence imaging capabilities.

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Published
2024-12-08
Cited
How to Cite
Trusova, V., Tarabara, U., Karnaukhov, I., Zelinsky, A., Borts, B., Ushakov, I., Sidenko, L., & Gorbenko, G. (2024). Computational Study of Drug Delivery Systems with Radionuclide and Fluorescence Imaging Modalities. I. Albumin-Based Systems for Doxorubicin Delivery. East European Journal of Physics, (4), 447-453. https://doi.org/10.26565/2312-4334-2024-4-54
Issue
No. 4 (2024): East European Journal of Physics
Section
Original Papers

Copyright (c) 2024 V. Trusova, U. Tarabara, I. Karnaukhov, A. Zelinsky, B. Borts, I. Ushakov, L. Sidenko, G. Gorbenko

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