In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

Andrea Angelo Pierluigi Tripodi, Ivan Ranđelović, Beáta Biri-Kovács, Bálint Szeder, Gábor Mező, József Tóvári

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi’s Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.

Original languageEnglish
Pages (from-to)1879-1892
Number of pages14
JournalPathology and Oncology Research
Volume26
Issue number3
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Antiangiogenic effect
  • CD13
  • Metastasis
  • NGR peptides
  • Targeted tumor therapy
  • Tumor growth inhibition

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