Anti-IL-1RAP scFv-mSA-S19-TAT fusion carrier as a multifunctional platform for versatile delivery of biotinylated payloads to myeloid leukemia cells.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 10 2024
Historique:
received: 16 08 2024
accepted: 17 10 2024
medline: 24 10 2024
pubmed: 24 10 2024
entrez: 24 10 2024
Statut: epublish

Résumé

Acute myeloid leukemia (AML) is an aggressive blood cancer with frequently poor clinical outcomes. This heterogeneous malignancy encompasses genetically, molecularly, and even clinically different subgroups. This makes it difficult to develop therapeutic agents that are effective for all subtypes of the disease. Therefore, a selective, universal, and adaptable delivery platform capable of carrying various types of anti-neoplastic agents is an unmet requirement in this area. Two multifunctional fusion proteins were designed for the delivery of biotinylated cargoes to human myeloid leukemia cells by fusing an anti-IL-1RAP single-chain antibody with streptavidin (tetramer or monomer), a cell-penetrating peptide (CPP), and an endosomolytic peptide in a single biomacromolecule. The designed fusions were analyzed primarily in silico, and the biofunctionality of the selected fusion was fully characterized via several binding assays, hemolysis assay, confocal microscopy and cell cytotoxicity assay after production via the Escherichia coli (E. coli) system. The refolded protein exhibited desirable binding activity to leukemic cells, pure antigen and biotinylated BSA. Further analyses revealed efficient cellular uptake, endosomolytic activity, and nuclear penetration without any detectable cytotoxicity toward normal epithelial cells. The described platform seems to have great potential for targeted delivery of different therapeutics to malignant myeloid cells.

Identifiants

pubmed: 39443595
doi: 10.1038/s41598-024-76851-7
pii: 10.1038/s41598-024-76851-7
doi:

Substances chimiques

Single-Chain Antibodies 0
Recombinant Fusion Proteins 0
Cell-Penetrating Peptides 0
Streptavidin 9013-20-1
Drug Carriers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

25080

Subventions

Organisme : Pasteur Institute of Iran
ID : BD-9365
Organisme : Iran National Science Foundation
ID : 96011491

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Aref Farokhi-Fard (A)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Saman Rahmati (S)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Division of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.

Negin Sadat Hashemi Aval (NS)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Farzaneh Barkhordari (F)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Elham Bayat (E)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Samira Komijani (S)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Hooman Aghamirza Moghim Aliabadi (H)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Fatemeh Davami (F)

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. F.davami@gmail.com.
Pasteur Institute of Iran, No. 69, Pasteur Ave, Tehran, Iran. F.davami@gmail.com.

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