TY - JOUR
T1 - In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery
AU - Tripodi, Andrea Angelo Pierluigi
AU - Ranđelović, Ivan
AU - Biri-Kovács, Beáta
AU - Szeder, Bálint
AU - Mező, Gábor
AU - Tóvári, József
N1 - Funding Information:
Open access funding provided by National Institute of Oncology (OOI). This work was supported by the National Research, Development and Innovation Office under grant NKFIH K116295 (J.T), K119552 (G.M.) and NVKP_16-1-2016-0036 (G.M), and by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant No 642004 (A.A.P.T., I.R., G.M., J.T.). This research was completed in the ELTE Institutional Excellence Program (1783-3/2018/FEKUTSRAT) supported by the Hungarian Ministry of Human Capacities (B.B-K.). These studies were also supported by grant (VEKOP-2.3.3-15-2017-00020) from the European Union and the State of Hungary, co-financed by the European Regional Development Fund (G.M). Financial support from the 2019 Thematic Excellence Program (TUDFO/51757/2019-ITM) (J.T.) is greatly acknowledged. Acknowledgements
Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Antiangiogenic effect
KW - CD13
KW - Metastasis
KW - NGR peptides
KW - Targeted tumor therapy
KW - Tumor growth inhibition
UR - http://www.scopus.com/inward/record.url?scp=85076736444&partnerID=8YFLogxK
U2 - 10.1007/s12253-019-00773-3
DO - 10.1007/s12253-019-00773-3
M3 - Article
C2 - 31820302
AN - SCOPUS:85076736444
SN - 1219-4956
VL - 26
SP - 1879
EP - 1892
JO - Pathology and Oncology Research
JF - Pathology and Oncology Research
IS - 3
ER -