posted on 2023-12-21, 13:33authored byRoman V. Timoshenko, Petr V. Gorelkin, Alexander N. Vaneev, Olga O. Krasnovskaya, Roman A. Akasov, Anastasiia S. Garanina, Dmitry A. Khochenkov, Tamara M. Iakimova, Natalia L. Klyachko, Tatiana O. Abakumova, Vera S. Shashkovskaya, Kirill D. Chaprov, Alexander A. Makarov, Vladimir A. Mitkevich, Yasufumi Takahashi, Christopher R.
W. Edwards, Yuri E. Korchev, Alexander S. Erofeev
In vitro/in vivo detection of copper ions is a challenging
task
but one which is important in the development of new approaches to
the diagnosis and treatment of cancer and hereditary diseases such
as Alzheimer’s, Wilson’s, etc. In this paper, we present
a nanopipette sensor capable of measuring Cu2+ ions with
a linear range from 0.1 to 10 μM in vitro and in vivo. Using
the gold-modified nanopipette sensor with a copper chelating ligand,
we evaluated the accumulation ability of the liposomal form of an
anticancer Cu-containing complex at three levels of biological organization.
First, we detected Cu2+ ions in a single cell model of
human breast adenocarcinoma MCF-7 and in murine melanoma B16 cells.
The insertion of the nanoelectrode did not result in leakage of the
cell membrane. We then evaluated the distribution of the Cu-complex
in MCF-7 tumor spheroids and found that the diffusion-limited accumulation
was a function of the depth, typical for 3D culture. Finally, we demonstrated
the use of the sensor for Cu2+ ion detection in the brain
of an APP/PS1 transgenic mouse model of Alzheimer’s disease
and tumor-bearing mice in response to injection (2 mg kg–1) of the liposomal form of the anticancer Cu-containing complex.
Enhanced stability and selectivity, as well as distinct copper oxidation
peaks, confirmed that the developed sensor is a promising tool for
testing various types of biological systems. In summary, this research
has demonstrated a minimally invasive electrochemical technique with
high temporal resolution that can be used for the study of metabolism
of copper or copper-based drugs in vitro and in vivo.