Human Serum Albumin Labelling with a New BODIPY Dye Having a Large Stokes Shift.

Valeria I Raskolupova,Olga D Zakharova,Vladimir N Silnikov,Tatyana V Abramova,Anastasia E Nikotina,Tatyana V Popova

doi:10.3390/molecules26092679

Abstract

BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials, and molecular probes. At the same time, BODIPY dyes have small or moderate Stokes shifts like most other fluorophores. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. The new boron containing BODIPY dye was designed and synthesized. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. This BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. BODIPY residue equipped with a suitable targeting protein core can be used as a suitable imaging probe and agent for Boron Neutron Capture Therapy (BNCT). As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal constructions. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA were labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis, and fluorescent emission spectra. Cytotoxicity of the resulting conjugate was investigated. This study is the basis for a novel BODIPY dye-albumin theranostic for BNCT. The results provide further impetus to develop derivatives of HSA for delivery of boron to cancer cells.

Highlights

The results provide further impetus to develop derivatives of human serum albumin (HSA) for delivery of boron to cancer cells
Boron neutron capture therapy (BNCT) is a promising cancer treatment modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that have a cell killing effect within a 10-μm range [1]
This study was directed toward the development of the HSA-based multimodal platform for the creation of a new BODIPY containing HSA-based theranostic with improved spectral properties for Boron Neutron Capture Therapy (BNCT)

Summary

Introduction

Boron neutron capture therapy (BNCT) is a promising cancer treatment modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that have a cell killing effect within a 10-μm range [1]. Successful BNCT mainly depends on the selective accumulation of 10B including agents in tumor cells. Only two boron agents, boronophenylalanine (BPA) and borocaptate sodium (BSH), have been used clinically [2,3,4]. Both compounds do not meet all the required criteria. Due to continuous blood circulation and low immunological effect, human serum albumin (HSA) is successfully used as a core to improve the potential of therapeutic agents in theranostic constructions [7,8,9,10,11,12,13,14,15]. Theranostics may contain fluorescence residues for sensing [20]

Methods

Results

Conclusion