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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

2017; Wiley; Volume: 2; Issue: 17 Linguagem: Inglês

10.1002/slct.201701052

2365-6549

Arianna Pina, Alberto Dal Corso, Michele Caruso, Laura Belvisi, Daniela Arosio, Simone Zanella, Fabio Gasparri, Clara Albanese, Ulisse Cucchi, Ivan Fraietta, Aurelio Marsiglio, Luca Pignataro, Daniele Donati, Cesare Gennari,

HER2/EGFR in Cancer Research

ChemistrySelectVolume 2, Issue 17 p. 4759-4766 Full Paper Targeting Integrin αVβ3 with Theranostic RGD-Camptothecin Conjugates Bearing a Disulfide Linker: Biological Evaluation Reveals a Complex Scenario Arianna Pina, Arianna Pina Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. A. Dal Corso, Dr. A. Dal Corso Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Michele Caruso, Dr. Michele Caruso Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorProf. Dr. Laura Belvisi, Prof. Dr. Laura Belvisi Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Daniela Arosio, Dr. Daniela Arosio Istituto di Scienze e Tecnologie Molecolari (ISTM), CNR, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorSimone Zanella, Simone Zanella Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Fabio Gasparri, Dr. Fabio Gasparri Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Clara Albanese, Dr. Clara Albanese Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Ulisse Cucchi, Dr. Ulisse Cucchi Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Ivan Fraietta, Dr. Ivan Fraietta Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Aurelio Marsiglio, Dr. Aurelio Marsiglio Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Luca Pignataro, Dr. Luca Pignataro Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Daniele Donati, Dr. Daniele Donati Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorProf. Dr. Cesare Gennari, Corresponding Author Prof. Dr. Cesare Gennari cesare.gennari@unimi.it orcid.org/0000-0002-7635-4900 Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this author Arianna Pina, Arianna Pina Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. A. Dal Corso, Dr. A. Dal Corso Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Michele Caruso, Dr. Michele Caruso Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorProf. Dr. Laura Belvisi, Prof. Dr. Laura Belvisi Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Daniela Arosio, Dr. Daniela Arosio Istituto di Scienze e Tecnologie Molecolari (ISTM), CNR, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorSimone Zanella, Simone Zanella Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Fabio Gasparri, Dr. Fabio Gasparri Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Clara Albanese, Dr. Clara Albanese Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Ulisse Cucchi, Dr. Ulisse Cucchi Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Ivan Fraietta, Dr. Ivan Fraietta Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Aurelio Marsiglio, Dr. Aurelio Marsiglio Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorDr. Luca Pignataro, Dr. Luca Pignataro Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this authorDr. Daniele Donati, Dr. Daniele Donati Nerviano Medical Sciences (NMS), Via Pasteur 10, 20014 Nerviano, ItalySearch for more papers by this authorProf. Dr. Cesare Gennari, Corresponding Author Prof. Dr. Cesare Gennari cesare.gennari@unimi.it orcid.org/0000-0002-7635-4900 Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milano, ItalySearch for more papers by this author First published: 14 June 2017 https://doi.org/10.1002/slct.201701052Citations: 13Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract All that glitters ain′t gold! A quite complex scenario is unveiled in the course of the biological evaluation of theranostic RGD-camptothecin conjugates, possessing a disulfide linker and a fluorescent naphthalimide moiety. Abstract 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 αVβ3-integrin receptor. For antiproliferative assays, the U87 human glioblastoma were chosen as αVβ3-expressing cells, whereas a non αVβ3-expressing clone (U87 β3-KO) was generated as negative control. Although the U87 β3-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 β3-KO clone. Conflict of interest The authors declare no conflict of interest. Citing Literature Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Filename Description slct201701052-sup-0001-misc_information.pdf1.7 MB Supplementary Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume2, Issue17June 12, 2017Pages 4759-4766 RelatedInformation