TY - JOUR

T1 - Homocystamide conjugates of human serum albumin as a platform to prepare bimodal multidrug delivery systems for boron neutron capture therapy

AU - Popova, Tatyana

AU - Dymova, Maya A.

AU - Koroleva, Ludmila S.

AU - Zakharova, Olga D.

AU - Lisitskiy, Vladimir A.

AU - Raskolupova, Valeria I.

AU - Sycheva, Tatiana

AU - Taskaev, Sergei

AU - Silnikov, Vladimir N.

AU - Godovikova, Tatyana S.

N1 - Funding Information: Funding: This research was funded by the Russian Science Foundation (grant №19-74-20123). Publisher Copyright: © 2021 by the authors.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)-a carrier protein with a long plasma half-life-is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro-closo-dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 µM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro-closo-dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imagingguided boron neutron capture therapy.

AB - Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)-a carrier protein with a long plasma half-life-is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro-closo-dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 µM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro-closo-dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imagingguided boron neutron capture therapy.

KW - Boron delivery agents

KW - Boron neutron capture therapy

KW - Boronated albumin theranostic

KW - Colony forming assay

KW - Conjugate

KW - In vitro efficacy evaluation

KW - Irradiated by epithermal neutron flux

KW - Thenoyltrifluoroacetone

KW - Boron Neutron Capture Therapy

KW - Humans

KW - Cell Survival/drug effects

KW - Antineoplastic Agents/chemical synthesis

KW - Drug Delivery Systems

KW - Boron Compounds/chemical synthesis

KW - Homocysteine/analogs & derivatives

KW - Cell Line, Tumor

KW - Molecular Structure

KW - Cell Proliferation/drug effects

KW - Serum Albumin, Human/chemistry

KW - Drug Screening Assays, Antitumor

UR - http://www.scopus.com/inward/record.url?scp=85120712909&partnerID=8YFLogxK

U2 - 10.3390/molecules26216537

DO - 10.3390/molecules26216537

M3 - Article

C2 - 34770947

AN - SCOPUS:85120712909

VL - 26

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 21

M1 - 6537

ER -