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• W4220807792 abstract "Si306, a pyrazolo[3,4-d]pyrimidine derivative recently identified as promising anticancer agent, has shown favorable in vitro and in vivo activity profile against neuroblastoma (NB) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, Si306 antitumor activity is associated with sub-optimal aqueous solubility, which might hinder its further development. Drug delivery systems were here developed with the aim to overcome this limitation, obtaining suitable formulations for more efficacious in vivo use. Si306 was encapsulated in pegylated stealth liposomes, undecorated or decorated with a monoclonal antibody able to specifically recognize and bind to the disialoganglioside GD2 expressed by NB cells (LP[Si306] and GD2-LP[Si306], respectively). Both liposomes possessed excellent morphological and physio-chemical properties, maintained over a period of two weeks. Compared to LP[Si306], GD2-LP[Si306] showed in vitro specific cellular targeting and increased cytotoxic activity against NB cell lines. After intravenous injection in healthy mice, pharmacokinetic profiles showed increased plasma exposure of Si306 when delivered by both liposomal formulations, compared to that obtained when Si306 was administered as free form. In vivo tumor homing and cytotoxic effectiveness of both liposomal formulations were finally tested in an orthotopic animal model of NB. Si306 tumor uptake resulted significantly higher when encapsulated in GD2-LP, compared to Si306, either free or encapsulated into untargeted LP. This, in turn, led to a significant increase in survival of mice treated with GD2-LP[Si306]. These results demonstrate a promising antitumor efficacy of Si306 encapsulated into GD2-targeted liposomes, supporting further therapeutic developments in pre-clinical trials and in the clinic for NB." @default.
• W4220807792 created "2022-04-03" @default.
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• W4220807792 date "2022-03-12" @default.
• W4220807792 modified "2023-10-18" @default.
• W4220807792 title "The Pyrazolo[3,4-d]Pyrimidine Derivative Si306 Encapsulated into Anti-GD2-Immunoliposomes as Therapeutic Treatment of Neuroblastoma" @default.
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• W4220807792 doi "https://doi.org/10.3390/biomedicines10030659" @default.
• W4220807792 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35327462" @default.

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