Speaker
Prof.
Vladimir Silnikov
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Description
As the most abundant protein with a variety of physiological functions, albumin has been used extensively for the delivery of therapeutic molecules. Our work focuses on optimizing the bioavailability of a probe by exploiting the inherent circulatory transport mechanisms of albumin. Herein, human serum albumin has been functionalized with a combination of maleimide of a fluorescent dye Cy7 and a fluorinated homocysteine thiolactone, yielding a dual-labeled molecular probe for 19F MRI and fluorescence imaging. The incubation of cells with this conjugate did not reveal any significant reduction in cell viability with respect to the unmodified albumin. Initial experiments in a glioma animal model showed that the tumor uptake of the dual-labeled albumin for 24 h after injection was higher than in the surrounding healthy brain tissues.
We report on the synthesis of homocystamide conjugates of the protein and their use in thiol-‘click’ chemistry to prepare of multimodal boron-albumin conjugates. A dual-labeled albumin-based molecular probe for 19F MRI and fluorescence microscopy has been obtained by functionalizing the protein with maleimide of a fluorescent dye and a fluorinated thiolactone derivative. The procedure of boron labeling has involved modifying the released sulfhydryl group of a homocysteine functional handle in the albumin structure by an undecahydro-closo-dodecaborate reagent. The successful preparation of boron-containing albumins were confirmed by MALDI-TOF-MS, inductively coupled plasma atomic emission spectroscopy, UV-Vis and fluorescent emission spectra. So, combined with the current technologies, we are now in a position to develop protein-based boron carriers with multiple functions, such as for in vivo imaging and active targeting in boron neutron capture therapy. This simple, and yet elegant, approach will benefit the field of nanomedicine which has been suffering from its limited success in clinical settings.
This work was supported by Russian Scientific Foundation grant 19-74-20123
Primary author
Prof.
Vladimir Silnikov
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Co-authors
Dr
Andrey Akulov
(Institute of Cytology and Genetics, SB RAS)
Dr
Evgenii Zavjalov
(Institute of Cytology and Genetics, SB RAS)
Mr
Georgii Panasenko
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Dr
Lyudmila Koroleva
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Dr
Oleg Shevelev
(Institute of Cytology and Genetics, SB RAS)
Dr
Olga Zakharova
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Prof.
Sergey Taskaev
(Budker Institute of Nuclear Physics, SB RAS)
Prof.
Tatyana Godovikova
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Dr
Tatyana Popova
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
Mr
Vladimir Lisitskiy
(Institute of Chemical Biology and Fundamental Medicine, SB RAS)
