Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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. и др.
в: Bioorganic and Medicinal Chemistry Letters, Том 27, № 16, 15.08.2017, стр. 3925-3930.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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.
N1 - Publisher Copyright: © 2017 Elsevier Ltd
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 -
ID: 8688654