Dopamine D<sub>2</sub> and Serotonin 5-HT<sub>1A</sub> Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain
Agata Kowalik,
Mateusz Majerek,
Krzysztof Mrowiec,
Joanna Solich,
Agata Faron-Górecka,
Olga Woźnicka,
Marta Dziedzicka-Wasylewska,
Sylwia Łukasiewicz
Affiliations
Agata Kowalik
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Mateusz Majerek
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Krzysztof Mrowiec
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Joanna Solich
Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland
Agata Faron-Górecka
Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland
Olga Woźnicka
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Krakow, Poland
Marta Dziedzicka-Wasylewska
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Sylwia Łukasiewicz
Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Targeted therapy uses multiple ways of ensuring that the drug will be delivered to the desired site. One of these ways is an encapsulation of the drug and functionalization of the surface. Among the many molecules that can perform such a task, the present work focused on the antibodies of single-chain variable fragments (scFvs format). We studied scFv, which specifically recognizes the dopamine D2 and serotonin 5-HT1A receptor heteromers. The scFvD2–5-HT1A protein was analyzed biochemically and biologically, and the obtained results indicated that the antibody is properly folded and non-toxic and can be described as low-immunogenic. It is not only able to bind to the D2–5-HT1A receptor heteromer, but it also influences the cAMP signaling pathway and—when surfaced on nanogold particles—it can cross the blood–brain barrier in in vitro models. When administered to mice, it decreased locomotor activity, matching the effect induced by clozapine. Thus, we are strongly convinced that scFvD2–5-HT1A, which was a subject of the present investigation, is a promising targeting ligand with the potential for the functionalization of nanocarriers targeting selected areas of the brain.
