Homocystamide Conjugates of Human Serum Albumin as a Platform to Prepare Bimodal Multidrug Delivery Systems for Boron Neutron Capture Therapy

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 21; p. 6537
• Main Authors: Popova, Tatyana, Dymova, Maya A., Koroleva, Ludmila S., Zakharova, Olga D., Lisitskiy, Vladimir A., Raskolupova, Valeria I., Sycheva, Tatiana, Taskaev, Sergei, Silnikov, Vladimir N., Godovikova, Tatyana S.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.10.2021; MDPI
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Biodistribution; Boron; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Boron Compounds - therapeutic use; boron delivery agents; Boron Neutron Capture Therapy; boronated albumin theranostic; Brain cancer; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; conjugate; Cytotoxicity; Drug Delivery Systems; Drug Screening Assays, Antitumor; Drugs; Fluorine; Glioma; Homocysteine - analogs & derivatives; Homocysteine - chemistry; Humans; Hyperglycemia; in vitro efficacy evaluation; Magnetic resonance imaging; Molecular Structure; Proteins; Radiation; Serum Albumin, Human - chemistry; thenoyltrifluoroacetone; Tumors; conjugate; boron neutron capture therapy; thenoyltrifluoroacetone; colony forming assay; boronated albumin theranostic; irradiated by epithermal neutron flux; in vitro efficacy evaluation; boron delivery agents
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26216537

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 imaging-guided boron neutron capture therapy.