Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery

Borbély AN, Figueras Agustí E, Martins A, Esposito S, Auciello G, Monteagudo E, Di Marco A, Summa V, Cordella P, Perego R, Kemker I, et al. (2019)
Pharmaceutics 11(4): 151.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Borbély, Adina NoémiUniBi; Figueras Agustí, EduardUniBi; Martins, Ana; Esposito, Simone; Auciello, Giulio; Monteagudo, Edith; Di Marco, Annalise; Summa, Vincenzo; Cordella, Paola; Perego, Raffaella; Kemker, IsabellUniBi; Frese, MarcelUniBi
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Abstract / Bemerkung
Cryptophycins are potent tubulin polymerization inhibitors with picomolar antiproliferative potency in vitro and activity against multidrug-resistant (MDR) cancer cells. Because of neurotoxic side effects and limited efficacy in vivo, cryptophycin-52 failed as a clinical candidate in cancer treatment. However, this class of compounds has emerged as attractive payloads for tumor-targeting applications. In this study, cryptophycin was conjugated to the cyclopeptide c(RGDfK), targeting integrin αvβ3, across the protease-cleavable Val-Cit linker and two different self-immolative spacers. Plasma metabolic stability studies in vitro showed that our selected payload displays an improved stability compared to the parent compound, while the stability of the conjugates is strongly influenced by the self-immolative moiety. Cathepsin B cleavage assays revealed that modifications in the linker lead to different drug release profiles. Antiproliferative effects of Arg-Gly-Asp (RGD)–cryptophycin conjugates were evaluated on M21 and M21-L human melanoma cell lines. The low nanomolar in vitro activity of the novel conjugates was associated with inferior selectivity for cell lines with different integrin αvβ3 expression levels. To elucidate the drug delivery process, cryptophycin was replaced by an infrared dye and the obtained conjugates were studied by confocal microscopy
Stichworte
antitumor agents; small molecule–drug conjugates; drug delivery; RGD peptides
Erscheinungsjahr
2019
Zeitschriftentitel
Pharmaceutics
Band
11
Ausgabe
4
Art.-Nr.
151
ISSN
1999-4923
eISSN
1999-4923
Page URI
https://pub.uni-bielefeld.de/record/2934762

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Borbély AN, Figueras Agustí E, Martins A, et al. Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery. Pharmaceutics. 2019;11(4): 151.
Borbély, A. N., Figueras Agustí, E., Martins, A., Esposito, S., Auciello, G., Monteagudo, E., Di Marco, A., et al. (2019). Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery. Pharmaceutics, 11(4), 151. doi:10.3390/pharmaceutics11040151
Borbély, A. N., Figueras Agustí, E., Martins, A., Esposito, S., Auciello, G., Monteagudo, E., Di Marco, A., Summa, V., Cordella, P., Perego, R., et al. (2019). Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery. Pharmaceutics 11:151.
Borbély, A.N., et al., 2019. Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery. Pharmaceutics, 11(4): 151.
A.N. Borbély, et al., “Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery”, Pharmaceutics, vol. 11, 2019, : 151.
Borbély, A.N., Figueras Agustí, E., Martins, A., Esposito, S., Auciello, G., Monteagudo, E., Di Marco, A., Summa, V., Cordella, P., Perego, R., Kemker, I., Frese, M., Gallinari, P., Steinkühler, C., Sewald, N.: Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery. Pharmaceutics. 11, : 151 (2019).
Borbély, Adina Noémi, Figueras Agustí, Eduard, Martins, Ana, Esposito, Simone, Auciello, Giulio, Monteagudo, Edith, Di Marco, Annalise, Summa, Vincenzo, Cordella, Paola, Perego, Raffaella, Kemker, Isabell, Frese, Marcel, Gallinari, Paola, Steinkühler, Christian, and Sewald, Norbert. “Synthesis and Biological Evaluation of RGD–Cryptophycin Conjugates for Targeted Drug Delivery”. Pharmaceutics 11.4 (2019): 151.
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Octreotide Conjugates for Tumor Targeting and Imaging.
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Dissertation, die diesen PUB Eintrag enthält
Conjugates of Cryptophycin and RGD Peptides for Targeted Cancer Therapy
Borbély AN (2019)
Bielefeld: Universität Bielefeld.

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