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Targeting Integrin α V β 3 with Theranostic RGD‐Camptothecin Conjugates Bearing a Disulfide Linker: Biological Evaluation Reveals a Complex Scenario
Author(s) -
Pina Arianna,
Dal Corso A.,
Caruso Michele,
Belvisi Laura,
Arosio Daniela,
Zanella Simone,
Gasparri Fabio,
Albanese Clara,
Cucchi Ulisse,
Fraietta Ivan,
Marsiglio Aurelio,
Pignataro Luca,
Donati Daniele,
Gennari Cesare
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201701052
Subject(s) - camptothecin , linker , internalization , moiety , u87 , chemistry , conjugate , integrin , cell culture , biophysics , clone (java method) , cell , biochemistry , stereochemistry , biology , dna , mathematical analysis , genetics , mathematics , computer science , operating system
Theranostic RGD‐camptothecin conjugates, possessing a disulfide linker and a fluorescent naphthalimide moiety, were synthesized and biologically evaluated. The conjugates showed nanomolar affinity for the purified α V β 3 ‐integrin receptor. For antiproliferative assays, the U87 human glioblastoma were chosen as α V β 3 ‐expressing cells, whereas a non α V β 3 ‐expressing clone (U87 β 3 ‐KO) was generated as negative control. Although the U87 β 3 ‐KO cells treated with the conjugates showed a statistically significant reduced fluorescence intensity (in the range 7–12 %) compared to the parental U87, internalization of the conjugates was clearly observed in both cell lines. Stability studies showed premature cleavage of the disulfide linker in the cell media, with consequent release of free camptothecin. Consistent with the results of the internalization and stability studies, the conjugates did not show significant selectivity against the U87 cells compared to the U87 β 3 ‐KO clone.