Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid)

Pechar, Michal; Král, Vlastimil; Kracíková, Lucie; Androvič, Ladislav; Hrdá, Eliška; Pola, Robert; Pytlíková, Sára; Studenovský, Martin; Kostka, Libor; Šubr, Vladimír; Etrych, Tomáš; Kočková, Olga; Ferreira Mendes, Jessica Marianne; Fábry, Milan; Laga, Richard

doi:https://dx.doi.org/10.1016/j.ijpharm.2023.123619

Number of the records: 1

Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid)

1.

SYSNO ASEP	0578323
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid)
Author(s)	Pechar, Michal (UMCH-V)_{RID, ORCID} Král, Vlastimil (UOCHB-X) Kracíková, Lucie (UMCH-V)_ORCID Androvič, Ladislav (UMCH-V)_ORCID Hrdá, Eliška (UMCH-V) Pola, Robert (UMCH-V)_{RID, ORCID} Pytlíková, Sára (UMCH-V) Studenovský, Martin (UMCH-V)_{RID, ORCID} Kostka, Libor (UMCH-V)_{RID, ORCID} Šubr, Vladimír (UMCH-V)_{RID, ORCID} Etrych, Tomáš (UMCH-V)_{RID, ORCID} Kočková, Olga (UMCH-V)_{RID, ORCID} Ferreira Mendes, Jessica Marianne (UOCHB-X) Fábry, Milan (UOCHB-X) Laga, Richard (UMCH-V)_{RID, ORCID}
Article number	123619
Source Title	International Journal of Pharmaceutics. - : Elsevier - ISSN 0378-5173 Roč. 648, 15 December (2023)
Number of pages	12 s.
Language	eng - English
Country	NL - Netherlands
Keywords	hydrophilic polymers ; thermo-responsive polymers ; polymer drug delivery system
Subject RIV	CD - Macromolecular Chemistry
OECD category	Polymer science
Subject RIV - cooperation	Institute of Organic Chemistry and Biochemistry
R&D Projects	LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UMCH-V - RVO:61389013 ; UOCHB-X - RVO:61388963
UT WOS	001119134300001
EID SCOPUS	85177570270
DOI	10.1016/j.ijpharm.2023.123619
Annotation	Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA. His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes. Those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.
Workplace	Institute of Macromolecular Chemistry
Contact	Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
Year of Publishing	2024
Electronic address	https://www.sciencedirect.com/science/article/pii/S0378517323010414?via%3Dihub

Number of the records: 1