Open AccessAuNP Pyrazolo[3,4-d]pyrimidine Nanosystem in Combination with Radiotherapy against Glioblastoma
Author(s) -
Alessio Molinari,
Giulia Iovenitti,
Arianna Mancini,
Giovanni Luca Gravina,
Mohsen Chebbi,
Maura Caruana,
Giulia Vignaroli,
Francesco Orofino,
Enrico Rango,
Adriano Angelucci,
Elena Dreassi,
Silvia Sche,
Maurizio Botta
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00538
Subject(s) - pyrimidine , conjugated system , colloidal gold , in vitro , glioblastoma , nanoparticle , chemistry , materials science , cancer research , nanotechnology , combinatorial chemistry , nuclear chemistry , medicine , stereochemistry , biochemistry , organic chemistry , polymer
Gold-nanoparticle (AuNP)-conjugated drugs represent a promising and innovative antitumor therapeutic approach. In our study, we describe the design, the synthesis, the preparation, and the characterization of AuNPs conjugated with the pyrazolo[3,4- d ]pyrimidine derivative SI306, a c-Src inhibitor. AuNPs-SI306 showed a good loading efficacy (65%), optimal stability in polar media and in human plasma, and a suitable morphological profile: a ζ-potential of -43.9 mV, a nanoparticle diameter of 48.6 nm, and a 0.441 PDI value. The antitumoral activity of AuNPs-SI306 was evaluated in vitro in the glioblastoma model, by the low-density growth assay, and also in combination with radiotherapy (RT). Results demonstrated that AuNPs had a basal radiosensitization ability and that AuNPs-SI306, when used in combination with RT, were more effective in inhibiting tumor cell growth with respect to AuNPs and free SI306.