TY - JOUR

T1 - Chemotherapeutic Boron-Containing Homocysteinamides of Human Serum Albumin

AU - Wang, M.

AU - Tsyrempilov, S. A.

AU - Moskalev, I. A.

AU - Zakharova, O. D.

AU - Kasatova, A. I.

AU - Sil’nikov, V. N.

AU - Godovikova, T. S.

AU - Popova, T. V.

N1 - The research was funded through the State Assignment for the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences (no. 121031300042-1). Chemotherapeutic Boron-Containing Homocysteinamides of Human Serum Albumin / M. Wang, S. A. Tsyrempilov, I. A. Moskalev [et al.] // Russian Journal of Bioorganic Chemistry. – 2025. – Vol. 51, No. 1. – P. 354-371. – DOI 10.1134/S1068162025010297.

PY - 2025/2/12

Y1 - 2025/2/12

N2 - Abstract: Objective: A combination of boron neutron capture therapy and chemotherapy can ensure good efficacy in cancer treatment. The development of therapeutic constructs that combine these two functions, specifically the possibility of in vitro and in vivo visualization and a convenient platform for selective delivery to the tumor, is of great relevance today. Methods: In this study, we focused on human serum albumin, a well-known drug delivery platform, and developed, based on albumin functionalized with boron clusters, therapeutic constructs, which as analogs of the chemotherapeutic molecule gemcitabine and signaling molecules. To create such constructs, we developed new analogs of homocysteine thiolactone containing closo-dodecaborate or cobalt bis(dicarbollide) and a gemcitabine analog containing closo-dodecaborate attached to the C5 carbon atom of the nitrogenous base. Results and Discussion: It was demonstrated that the the conjugates modified with the gemcitabine analogs exhibit increased cytotoxicity against human glioblastoma cell lines. Among the obtained conjugates, the highest cytotoxicity is demonstrated by that containing cobalt bis(dicarbollide). The resulting structures accumulate well in the cytoplasm of cancer cells. The albumin conjugate containing cobalt bis(dicarbollide) and the boron-containing gemcitabine analog is capable of accumulating in the nuclei of T98G cell lines. Conclusions: The resulting albumin constructs showed sufficient in vitro activity against human glioma cells. It is expected that the obtained therapeutic conjugates will significantly enhance the anticancer efficacy of irradiation with epithermal neutrons. Combining a chemotherapeutic residue and a boron-containing group in a single construct provides potential for more effective glioma therapy.

AB - Abstract: Objective: A combination of boron neutron capture therapy and chemotherapy can ensure good efficacy in cancer treatment. The development of therapeutic constructs that combine these two functions, specifically the possibility of in vitro and in vivo visualization and a convenient platform for selective delivery to the tumor, is of great relevance today. Methods: In this study, we focused on human serum albumin, a well-known drug delivery platform, and developed, based on albumin functionalized with boron clusters, therapeutic constructs, which as analogs of the chemotherapeutic molecule gemcitabine and signaling molecules. To create such constructs, we developed new analogs of homocysteine thiolactone containing closo-dodecaborate or cobalt bis(dicarbollide) and a gemcitabine analog containing closo-dodecaborate attached to the C5 carbon atom of the nitrogenous base. Results and Discussion: It was demonstrated that the the conjugates modified with the gemcitabine analogs exhibit increased cytotoxicity against human glioblastoma cell lines. Among the obtained conjugates, the highest cytotoxicity is demonstrated by that containing cobalt bis(dicarbollide). The resulting structures accumulate well in the cytoplasm of cancer cells. The albumin conjugate containing cobalt bis(dicarbollide) and the boron-containing gemcitabine analog is capable of accumulating in the nuclei of T98G cell lines. Conclusions: The resulting albumin constructs showed sufficient in vitro activity against human glioma cells. It is expected that the obtained therapeutic conjugates will significantly enhance the anticancer efficacy of irradiation with epithermal neutrons. Combining a chemotherapeutic residue and a boron-containing group in a single construct provides potential for more effective glioma therapy.

KW - boron delivery systems

KW - boron neutron capture therapy

KW - boron-containing gemcitabine analogs

KW - boron-containing homocysteine thiolactone analogs

KW - theranostic conjugates of borated albumin

UR - https://www.mendeley.com/catalogue/3ba141c0-89ad-3d16-9a03-2c78000ef66f/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85218815285&origin=inward&txGid=50c1e7337c0cd1c40685e038aac6ba23

UR - https://elibrary.ru/item.asp?id=80320843

U2 - 10.1134/S1068162025010297

DO - 10.1134/S1068162025010297

M3 - Article

VL - 51

SP - 354

EP - 371

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 1

ER -