1. Plasmin-Binding Tripeptide-Decorated Liposomes Loading Pyrazolo[3,4-d]pyrimidines for Targeting Hepatocellular Carcinoma
- Author
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Francesca Candita, Mario Chiariello, Pierpaolo Calandro, Adriano Angelucci, Elena Dreassi, Arianna Mancini, Silvia Schenone, Maurizio Botta, Claudio Zamperini, and Giulia Iovenitti
- Subjects
0301 basic medicine ,Hepatocellular carcinoma, active-targeted liposomes, pyrazolo[3,4-d]pyrimidines, plasmin ,Hepatocellular carcinoma ,Plasmin ,Cell ,pyrazolo[3 ,Tripeptide ,Biochemistry ,active-targeted liposomes ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Tyrosine ,4- d]pyrimidines ,plasmin ,Liposome ,Kinase ,Chemistry ,Drug Discovery3003 Pharmaceutical Science ,Organic Chemistry ,digestive system diseases ,In vitro ,030104 developmental biology ,medicine.anatomical_structure ,4-d]pyrimidines ,030220 oncology & carcinogenesis ,pyrazolo[3,4- d]pyrimidines ,Tyrosine kinase ,medicine.drug - Abstract
[Image: see text] Hepatocellular carcinoma (HCC) is one of the most fatal cancer types worldwide. HCC cells were proved to overexpress c-Src and Sgk1, a tyrosine and a serine-threonine kinase, respectively, whose role is crucial for the development and progression of the tumor. Pyrazolo[3,4-d]pyrimidine derivatives are a class of tyrosine kinase inhibitors that have shown good activity against HepG2. HCC cells were also proved to overexpress plasmin, which is localized on the cell surface bound to its receptors. In this study, a tripeptide with sequence d-Ala-Phe-Lys, which binds a specific reactive site of plasmin, was synthesized and characterized. This tripeptide was used to decorate liposomes encapsulating three selected pyrazolo[3,4-d]pyrimidines. Liposomes bearing tripeptide have been characterized, not showing remarkable differences with respect to the corresponding tripeptide-free liposomes. In vitro HepG2 cell uptake profiles and cytotoxicities showed that the presence of the tripeptide on the liposomal membrane surface improves the cell-penetrating ability of liposomes and increases the activity of two of the three tested compounds.
- Published
- 2018