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Peptide‐Driven Targeted Drug‐Delivery System Comprising Turn‐On Near‐Infrared Fluorescent Xanthene–Cyanine Reporter for Real‐Time Monitoring of Drug Release
Author(s) -
Ebaston T. M.,
Rozovsky Alex,
Zaporozhets Alisa,
Bazylevich Andrii,
Tuchinsky Helena,
Marks Vered,
Gellerman Gary,
Patsenker Leonid D.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900464
Subject(s) - cyanine , linker , chemistry , drug delivery , fluorescence , xanthene , targeted drug delivery , conjugate , biophysics , biochemistry , biology , photochemistry , mathematical analysis , physics , mathematics , organic chemistry , quantum mechanics , computer science , operating system
Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real‐time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near‐infrared (NIR) fluorescence signal for the detection of drug‐release events. Herein, a new TDD system, comprising a turn‐on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug‐release events in target tissue. In this TDD system, a new carboxy‐derivatized xanthene–cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR‐2 and STTR‐5 overexpressed on many tumor cells. This OCTA‐G‐XCy‐CLB (G: γ‐aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ ≈710 nm; this signals release of the drug. Real‐time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR‐2 and STTR‐5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.