Molinari Alessio, Iovenitti Giulia, Mancini Arianna, Gravina Giovanni Luca, Chebbi Monia, Caruana Maura, Vignaroli Giulia, Orofino Francesco, Rango Enrico, Angelucci Adriano, Dreassi Elena, Schenone Silvia, Botta Maurizio
Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 12, 56126 Pisa, Italy.
ACS Med Chem Lett. 2020 Mar 5;11(5):664-670. doi: 10.1021/acsmedchemlett.9b00538. eCollection 2020 May 14.
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-]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 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.
金纳米颗粒（AuNP）偶联药物是一种很有前景的创新型抗肿瘤治疗方法。在我们的研究中，我们描述了与吡唑并[3,4 -]嘧啶衍生物SI306（一种c-Src抑制剂）偶联的金纳米颗粒的设计、合成、制备及表征。AuNPs-SI306表现出良好的负载效率（65%）、在极性介质和人血浆中的最佳稳定性以及合适的形态特征：ζ电位为-43.9 mV，纳米颗粒直径为48.6 nm，多分散指数（PDI）值为0.441。通过低密度生长试验在胶质母细胞瘤模型中评估了AuNPs-SI306的抗肿瘤活性，并且还评估了其与放射治疗（RT）联合使用时的活性。结果表明，金纳米颗粒具有基础放射增敏能力，并且当AuNPs-SI306与RT联合使用时，相对于金纳米颗粒和游离SI306，在抑制肿瘤细胞生长方面更有效。
