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

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

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Номер статьи6537
ЖурналMolecules
Том26
Номер выпуска21
DOI
СостояниеОпубликовано - 1 ноя 2021

Предметные области OECD FOS+WOS

  • 1.06.CQ БИОХИМИЯ И МОЛЕКУЛЯРНАЯ БИОЛОГИЯ
  • 1.04 ХИМИЧЕСКИЕ НАУКИ

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