Protein Corona Attenuates the Targeting of Antitumor Sialyl Lewis X-Decorated Liposomes to Vascular Endothelial Cells under Flow Conditions.

Natalia R Onishchenko, Alexey A Moskovtsev, Maria K Kobanenko, Daria S Tretiakova, Anna S Alekseeva, Dmitry V Kolesov, Anna A Mikryukova, Ivan A Boldyrev, Marina R Kapkaeva, Olga N Shcheglovitova, Nicolai V Bovin, Aslan A Kubatiev, Olga V Tikhonova, Elena L Vodovozova
Author Information
  1. Natalia R Onishchenko: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID
  2. Alexey A Moskovtsev: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, ul. Baltiyskaya 8, 125315 Moscow, Russia.
  3. Maria K Kobanenko: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
  4. Daria S Tretiakova: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID
  5. Anna S Alekseeva: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID
  6. Dmitry V Kolesov: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, ul. Baltiyskaya 8, 125315 Moscow, Russia. ORCID
  7. Anna A Mikryukova: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, ul. Baltiyskaya 8, 125315 Moscow, Russia.
  8. Ivan A Boldyrev: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID
  9. Marina R Kapkaeva: N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, ul. Gamaleya 18, 123098 Moscow, Russia.
  10. Olga N Shcheglovitova: N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, ul. Gamaleya 18, 123098 Moscow, Russia.
  11. Nicolai V Bovin: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID
  12. Aslan A Kubatiev: Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, ul. Baltiyskaya 8, 125315 Moscow, Russia.
  13. Olga V Tikhonova: Institute of Biomedical Chemistry, ul. Pogodinskaya 10, 119121 Moscow, Russia. ORCID
  14. Elena L Vodovozova: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia. ORCID

Abstract

Previously, we showed in the human umbilical vein endothelial cells (HUVECs) model that a liposome formulation of melphalan lipophilic prodrug (MlphDG) decorated with selectin ligand tetrasaccharide Sialyl Lewis X (SiaLe) undergoes specific uptake by activated cells and in an in vivo tumor model causes a severe antivascular effect. Here, we cultured HUVECs in a microfluidic chip and then applied the liposome formulations to study their interactions with the cells in situ under hydrodynamic conditions close to capillary blood flow using confocal fluorescent microscopy. The incorporation of 5 to 10% SiaLe conjugate in the bilayer of MlphDG liposomes increased their consumption exclusively by activated endotheliocytes. The increase of serum concentration from 20 to 100% in the flow resulted in lower liposome uptake by the cells. To elucidate the possible roles of plasma proteins in the liposome-cell interactions, liposome protein coronas were isolated and analyzed by shotgun proteomics and immunoblotting of selected proteins. Proteomic analysis showed that a gradual increase in SiaLe content correlated with the overall enrichment of the liposome-associated proteins with several apolipoproteins, including the most positively charged one, ApoC1, and serum amyloid A4, associated with inflammation, on the one hand, and a decrease in the content of bound immunoglobulins, on the other. The article discusses the potential interference of the proteins in the binding of liposomes to selectins of endothelial cells.

Keywords

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Grants

  1. 21-74-20177/Russian Science Foundation
  2. 19-015-00499/Russian Foundation for Basic Research

Word Cloud

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