TY - JOUR
T1 - Targeting Delivery of Platelets Inhibitor to Prevent Tumor Metastasis
AU - Geranpayehvaghei, Marzieh
AU - Shi, Quanwei
AU - Zhao, Baochang
AU - Li, Suping
AU - Xu, Junchao
AU - Taleb, Mohammad
AU - Qin, Hao
AU - Zhang, Yinlong
AU - Khajeh, Khosro
AU - Nie, Guangjun
N1 - PMID: 31429535
PY - 2019/9/18
Y1 - 2019/9/18
N2 - Activated platelets have a high affinity for tumor cells, and consequently, they can protect tumor cells from environmental stress and immune attacks. Therefore, preventing platelet–tumor cell interaction can lead to the elimination of circulating tumor cells via natural killer cells and finally metastasis inhibition. It is also shown that CREKA (Cys-Arg-Glu-Lys-Ala), a tumor-homing pentapeptide, targets fibrin–fibronectin complexes that are found on the tumor stroma and the vessel walls. In this study, we linked CREKA to Ticagrelor, a reversible antagonist of the P2Y12 receptor on platelets. In vitro experiments indicated that CREKA-Ticagrelor could not only inhibit the platelet-induced migration of tumor cells with an invasive phenotype but also prevent tumor–platelet interaction. In vivo antitumor and antimetastasis results of this drug showed that CREKA-Ticagrelor could specifically target the tumor tissues within 24 h post intravenous injection and suppress lung metastasis. Meanwhile, by having this antiplatelet drug targeted, its side effects were minimized, and bleeding risk was decreased. Thus, CREKA-Ticagrelor offers an efficient antimetastatic agent.
AB - Activated platelets have a high affinity for tumor cells, and consequently, they can protect tumor cells from environmental stress and immune attacks. Therefore, preventing platelet–tumor cell interaction can lead to the elimination of circulating tumor cells via natural killer cells and finally metastasis inhibition. It is also shown that CREKA (Cys-Arg-Glu-Lys-Ala), a tumor-homing pentapeptide, targets fibrin–fibronectin complexes that are found on the tumor stroma and the vessel walls. In this study, we linked CREKA to Ticagrelor, a reversible antagonist of the P2Y12 receptor on platelets. In vitro experiments indicated that CREKA-Ticagrelor could not only inhibit the platelet-induced migration of tumor cells with an invasive phenotype but also prevent tumor–platelet interaction. In vivo antitumor and antimetastasis results of this drug showed that CREKA-Ticagrelor could specifically target the tumor tissues within 24 h post intravenous injection and suppress lung metastasis. Meanwhile, by having this antiplatelet drug targeted, its side effects were minimized, and bleeding risk was decreased. Thus, CREKA-Ticagrelor offers an efficient antimetastatic agent.
U2 - 10.1021/acs.bioconjchem.9b00457
DO - 10.1021/acs.bioconjchem.9b00457
M3 - Article
SN - 1043-1802
VL - 30
SP - 2349
EP - 2357
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 9
ER -