1. Peptide-Driven Targeted Drug-Delivery System Comprising Turn-On Near-Infrared Fluorescent Xanthene-Cyanine Reporter for Real-Time Monitoring of Drug Release.
- Author
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Ebaston TM, Rozovsky A, Zaporozhets A, Bazylevich A, Tuchinsky H, Marks V, Gellerman G, and Patsenker LD
- Subjects
- Aminobutyrates chemistry, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, CHO Cells, Carbocyanines metabolism, Cell Line, Tumor, Cell Survival drug effects, Chlorambucil pharmacology, Cricetulus, Drug Carriers metabolism, Fluorescent Dyes chemistry, Fluorescent Dyes metabolism, Gene Expression Regulation, Neoplastic, Humans, Molecular Targeted Therapy methods, Receptors, Somatostatin chemistry, Receptors, Somatostatin genetics, Xanthenes metabolism, Carbocyanines chemistry, Chlorambucil chemistry, Drug Carriers chemistry, Fluorenes chemistry, Octreotide metabolism, Resins, Synthetic chemistry, Xanthenes chemistry
- Abstract
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., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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