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

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Homocystamide conjugates of human serum albumin as a platform to prepare bimodal multidrug delivery systems for boron neutron capture therapy. / Popova, Tatyana; Dymova, Maya A.; Koroleva, Ludmila S. et al.

In: Molecules, Vol. 26, No. 21, 6537, 01.11.2021.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{7f1468db24814c269808cd7e7ce713a9,

title = "Homocystamide conjugates of human serum albumin as a platform to prepare bimodal multidrug delivery systems for boron neutron capture therapy",

abstract = "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-{\textquoteleft}click{\textquoteright} 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.",

keywords = "Boron delivery agents, Boron neutron capture therapy, Boronated albumin theranostic, Colony forming assay, Conjugate, In vitro efficacy evaluation, Irradiated by epithermal neutron flux, Thenoyltrifluoroacetone, Boron Neutron Capture Therapy, Humans, Cell Survival/drug effects, Antineoplastic Agents/chemical synthesis, Drug Delivery Systems, Boron Compounds/chemical synthesis, Homocysteine/analogs & derivatives, Cell Line, Tumor, Molecular Structure, Cell Proliferation/drug effects, Serum Albumin, Human/chemistry, Drug Screening Assays, Antitumor",

author = "Tatyana Popova and Dymova, {Maya A.} and Koroleva, {Ludmila S.} and Zakharova, {Olga D.} and Lisitskiy, {Vladimir A.} and Raskolupova, {Valeria I.} and Tatiana Sycheva and Sergei Taskaev and Silnikov, {Vladimir N.} and Godovikova, {Tatyana S.}",

note = "Funding Information: Funding: This research was funded by the Russian Science Foundation (grant №19-74-20123). Publisher Copyright: {\textcopyright} 2021 by the authors.",

year = "2021",

month = nov,

day = "1",

doi = "10.3390/molecules26216537",

language = "English",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "21",

}

RIS

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.

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 -

ID: 34929405