Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics

Lisitskiy, Vladimir A.; Khan, Hamda; Popova, Tatyana V.; Chubarov, Alexey S.; Zakharova, Olga D.; Akulov, Andrey E.; Shevelev, Oleg B.; Zavjalov, Evgenii L.; Koptyug, Igor V.; Мошкин, М. П.; Silnikov, Vladimir N.; Ahmad, Saheem; Godovikova, Tatyana S.

doi:10.1016/j.bmcl.2017.05.084

Cited by 31 publications

(54 citation statements)

References 31 publications

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“…HSA is the most abundant protein in blood plasma and is widely used as a drug carrier . Fullerenes show a great potential in numerous biological and medicinal applications and their binding with proteins enhances solubility in water and might facilitate transport to the target sites .…”

Section: Methodsmentioning

confidence: 99%

Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy

et al. 2019

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Precise nanoscale distance measurements by pulsed electron paramagnetic resonance (EPR) spectroscopy play a crucial role in structural studies of biomolecules. The properties of the spin labels used in this approach determine the sensitivity limits, attainable distances, and proximity to biological conditions. Herein, we propose and validate the use of photoexcited fullerenes as spin labels for pulsed dipolar (PD) EPR distance measurements. Hyperpolarization and the narrower spectrum of fullerenes compared to other triplets (e.g., porphyrins) boost the sensitivity, and superior relaxation properties allow PD EPR measurements up to a near‐room temperature. This approach is demonstrated using fullerene–nitroxide and fullerene–triarylmethyl pairs, as well as a supramolecular complex of fullerene with nitroxide‐labeled protein. Photoexcited triplet fullerenes can be considered as new spin labels with outstanding spectroscopic properties for future structural studies of biomolecules.

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Section: Methodsmentioning

confidence: 99%

Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy

et al. 2019

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“…HSA readily crosses blood-vessel and blood-brain barriers and can accumulate in tumors; hence HSA conjugates can be injected remotely from sensitive organs/tissues and be delivered by the circulation. The properties of HSA are preserved when conjugated with HTL or its derivatives [40,47,77] (and see above), and could be exploited with ORCAs to specifically enhance contrast for tumors. HSA-based constructs often bind to albondin on the endothelium and SPARC in the tumor interstitium, thereby accumulating in and highlighting tumors, including brain tumors (glioma) [32,40,47,77,78].…”

Section: Characterization Of Hsa-nit Magnetic Propertiesmentioning

confidence: 99%

“…The properties of HSA are preserved when conjugated with HTL or its derivatives [40,47,77] (and see above), and could be exploited with ORCAs to specifically enhance contrast for tumors. HSA-based constructs often bind to albondin on the endothelium and SPARC in the tumor interstitium, thereby accumulating in and highlighting tumors, including brain tumors (glioma) [32,40,47,77,78]. Finally, the lifetime of HSA in the body is about 25 days with a normal turnover of more than 10 g per day [79], readily accommodating the HSA added by a conjugate optimized for use as an ORCA.…”

Section: Characterization Of Hsa-nit Magnetic Propertiesmentioning

confidence: 99%

Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

et al. 2020

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Four albumin-nitroxide conjugates were prepared and tested as metal-free organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). Each human serum albumin (HSA) carrier bears multiple nitroxides conjugated via homocysteine thiolactones. These molecular conjugates retain important physical and biological properties of their HSA component, and the resistance of their nitroxide groups to bioreduction was retained or enhanced. The relaxivities are similar for these four conjugates and are much greater than those of their individual components: the HSA or the small nitroxide molecules. This new family of conjugates has excellent prospects for optimization as ORCAs.

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“…Due to continuous blood circulation and low immunological effect HSA is successfully used as a core to improve the potential of therapeutic agents [12][13][14][15][16][17][18][19]. The binding of BODIPY residues to proteins is a rather recent topic for research.…”

Section: Bioconjugationmentioning

confidence: 99%

New BODIPY Dye with a Large Stokes Shift for Biopolymer Labelling

Raskolupova

Popova

Zakharova

et al. 2020

The 24th International Electronic Conference on Synthetic Organic Chemistry

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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 imaging probes and agents for Boron Neutron Capture Therapy (BNCT). For this purpose, boron containing BODIPY dye was designed and synthesized. 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. In the same time, BODIPY dyes as most other fluorophores have small or moderate Stokes shifts. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. 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. Moreover, this BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA was labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis and fluorescent emission spectra. The cytotoxicity of HSA conjugate was evaluated by MTT assay in cell lines MCF-7 and T98G. This is the basis for a novel BODIPY dye-albumin theranostic for BNCT. These results provide further impetus to develop derivatives of HSA for delivery of Boron to cancer cells.

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Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics

Cited by 31 publications

References 31 publications

Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy

Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy

Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents

New BODIPY Dye with a Large Stokes Shift for Biopolymer Labelling

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