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

Research output: Contribution to journalArticlepeer-review

9 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 languageEnglish
Pages (from-to)3925-3930
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number16
DOIs
Publication statusPublished - 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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