Abstract
AbstractAmong 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 andin vivoantitumor 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 toisoDGR in case of conjugate2(Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate1(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.
Funder
Horizon 2020
Nemzeti Kutatási Fejlesztési és Innovációs Hivatal
Nemzeti Kutatási és Technológiai Hivatal
The 2019 Thematic Excellence Program
European Union and the State of Hungary, co-financed by the European Regional Development Fund
South Carolina Center of Economic Excellence
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine,Pathology and Forensic Medicine
Cited by
20 articles.
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