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

作者：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; Moshkin Mikhail P; Silnikov Vladimir N; Ahmad Saheem; Godovikova Tatyana S^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(16): 3925-3930.

DOI：10.1016/j.bmcl.2017.05.084

• Theranostic prodrug
• Trifluorothymidine conjugate
• Modified human serum albumin
• Dual-responsive drug release
• Multimodal molecular imaging

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 F-19 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.

• 出版日期2017-8-15