Internalization of transferrin-tagged Myxococcus xanthus encapsulins into mesenchymal stem cells.

Autor:	Gabashvili AN; Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia., Alexandrushkina NA; Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russia.; Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia., Mochalova EN; Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia.; Moscow Center for Advanced Studies, Moscow, Russia.; Nanobiomedicine Division, Sirius University of Science and Technology, Sirius, Russia., Goliusova DV; Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow, Russia.; Laboratory of Cell Biology, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of FMBA, Moscow, Russia., Sapozhnikova EN; Moscow Center for Advanced Studies, Moscow, Russia., Makarevich PI; Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russia.; Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia., Nikitin PI; Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2024 May 07; Vol. 249, pp. 10055. Date of Electronic Publication: 2024 May 07 (Print Publication: 2024).
DOI:	10.3389/ebm.2024.10055
Abstrakt:	Currently, various functionalized nanocarrier systems are extensively studied for targeted delivery of drugs, peptides, and nucleic acids. Joining the approaches of genetic and chemical engineering may produce novel carriers for precise targeting different cellular proteins, which is important for both therapy and diagnosis of various pathologies. Here we present the novel nanocontainers based on vectorized genetically encoded Myxococcus xanthus (Mx) encapsulin, confining a fluorescent photoactivatable mCherry (PAmCherry) protein. The shells of such encapsulins were modified using chemical conjugation of human transferrin (Tf) prelabeled with a fluorescein-6 (FAM) maleimide acting as a vector. We demonstrate that the vectorized encapsulin specifically binds to transferrin receptors (TfRs) on the membranes of mesenchymal stromal/stem cells (MSCs) followed by internalization into cells. Two spectrally separated fluorescent signals from Tf-FAM and PAmCherry are clearly distinguishable and co-localized. It is shown that Tf-tagged Mx encapsulins are internalized by MSCs much more efficiently than by fibroblasts. It has been also found that unlabeled Tf effectively competes with the conjugated Mx-Tf-FAM formulations. That indicates the conjugate internalization into cells by Tf-TfR endocytosis pathway. The developed nanoplatform can be used as an alternative to conventional nanocarriers for targeted delivery of, e.g., genetic material to MSCs. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Gabashvili, Alexandrushkina, Mochalova, Goliusova, Sapozhnikova, Makarevich and Nikitin.)
Databáze:	MEDLINE
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