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

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

doi:10.1016/j.bmcl.2017.05.084

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

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

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13 Citations (Scopus)

Abstract

We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2′-deoxyuridine 5′-monophosphate (pTFT). The conjugate allows for direct optical and ¹⁹F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.

Original language	English
Pages (from-to)	3925-3930
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2017.05.084
Publication status	Published - 15 Aug 2017

Keywords

Dual-responsive drug release
Modified human serum albumin
Multimodal molecular imaging
Theranostic prodrug
Trifluorothymidine conjugate
Oxidation-Reduction
Serum Albumin/chemistry
Humans
Structure-Activity Relationship
Antineoplastic Agents/chemical synthesis
Dose-Response Relationship, Drug
Nucleotides/chemistry
Cell Line, Tumor
Thymine Nucleotides/chemistry
Molecular Structure
Cell Proliferation/drug effects
Drug Screening Assays, Antitumor
Hydrogen-Ion Concentration
ACTIVATION
THYMIDYLATE SYNTHASE
TRIFLUOROTHYMIDINE
INNOVATION
DELIVERY
INHIBITION
SOLID TUMORS
CHEMOTHERAPY
GEMCITABINE
TAS-102

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10.1016/j.bmcl.2017.05.084

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Lisitskiy, V. A., Khan, H., Popova, T. V., Chubarov, A. S., Zakharova, O. D., Akulov, A. E., Shevelev, O. B., Zavjalov, E. L., Koptyug, I. V., Moshkin, M. P., Silnikov, V. N., Ahmad, S., & Godovikova, T. S. (2017). Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics. Bioorganic and Medicinal Chemistry Letters, 27(16), 3925-3930. https://doi.org/10.1016/j.bmcl.2017.05.084

@article{d3c537b697ca436cac09962474cca162,

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

abstract = "We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2′-deoxyuridine 5′-monophosphate (pTFT). The conjugate allows for direct optical and 19F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.",

keywords = "Dual-responsive drug release, Modified human serum albumin, Multimodal molecular imaging, Theranostic prodrug, Trifluorothymidine conjugate, Oxidation-Reduction, Serum Albumin/chemistry, Humans, Structure-Activity Relationship, Antineoplastic Agents/chemical synthesis, Dose-Response Relationship, Drug, Nucleotides/chemistry, Cell Line, Tumor, Thymine Nucleotides/chemistry, Molecular Structure, Cell Proliferation/drug effects, Drug Screening Assays, Antitumor, Hydrogen-Ion Concentration, ACTIVATION, THYMIDYLATE SYNTHASE, TRIFLUOROTHYMIDINE, INNOVATION, DELIVERY, INHIBITION, SOLID TUMORS, CHEMOTHERAPY, GEMCITABINE, TAS-102",

author = "Lisitskiy, {Vladimir A.} and Hamda Khan and Popova, {Tatyana V.} and Chubarov, {Alexey S.} and Zakharova, {Olga D.} and Akulov, {Andrey E.} and Shevelev, {Oleg B.} and Zavjalov, {Evgenii L.} and Koptyug, {Igor V.} and Moshkin, {Mikhail P.} and Silnikov, {Vladimir N.} and Saheem Ahmad and Godovikova, {Tatyana S.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2017.05.084",

language = "English",

volume = "27",

pages = "3925--3930",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "16",

}

Lisitskiy, VA, Khan, H, Popova, TV, Chubarov, AS, Zakharova, OD, Akulov, AE, Shevelev, OB, Zavjalov, EL, Koptyug, IV, Moshkin, MP, Silnikov, VN, Ahmad, S & Godovikova, TS 2017, 'Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 16, pp. 3925-3930. https://doi.org/10.1016/j.bmcl.2017.05.084

TY - JOUR

T1 - Multifunctional human serum albumin-therapeutic nucleotide conjugate with redox and pH-sensitive drug release mechanism for cancer theranostics

AU - Lisitskiy, Vladimir A.

AU - Khan, Hamda

AU - Popova, Tatyana V.

AU - Chubarov, Alexey S.

AU - Zakharova, Olga D.

AU - Akulov, Andrey E.

AU - Shevelev, Oleg B.

AU - Zavjalov, Evgenii L.

AU - Koptyug, Igor V.

AU - Moshkin, Mikhail P.

AU - Silnikov, Vladimir N.

AU - Ahmad, Saheem

AU - Godovikova, Tatyana S.

PY - 2017/8/15

Y1 - 2017/8/15

N2 - We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2′-deoxyuridine 5′-monophosphate (pTFT). The conjugate allows for direct optical and 19F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.

AB - We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2′-deoxyuridine 5′-monophosphate (pTFT). The conjugate allows for direct optical and 19F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.

KW - Dual-responsive drug release

KW - Modified human serum albumin

KW - Multimodal molecular imaging

KW - Theranostic prodrug

KW - Trifluorothymidine conjugate

KW - Oxidation-Reduction

KW - Serum Albumin/chemistry

KW - Humans

KW - Structure-Activity Relationship

KW - Antineoplastic Agents/chemical synthesis

KW - Dose-Response Relationship, Drug

KW - Nucleotides/chemistry

KW - Cell Line, Tumor

KW - Thymine Nucleotides/chemistry

KW - Molecular Structure

KW - Cell Proliferation/drug effects

KW - Drug Screening Assays, Antitumor

KW - Hydrogen-Ion Concentration

KW - ACTIVATION

KW - THYMIDYLATE SYNTHASE

KW - TRIFLUOROTHYMIDINE

KW - INNOVATION

KW - DELIVERY

KW - INHIBITION

KW - SOLID TUMORS

KW - CHEMOTHERAPY

KW - GEMCITABINE

KW - TAS-102

UR - http://www.scopus.com/inward/record.url?scp=85021403313&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2017.05.084

DO - 10.1016/j.bmcl.2017.05.084

M3 - Article

C2 - 28676274

AN - SCOPUS:85021403313

VL - 27

SP - 3925

EP - 3930

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 16

ER -

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

Abstract

Keywords

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