New functionalized silica nanoparticles (SiNPs) as a potential daunorubicin delivery platform: an in vitro proof-of-concept evaluation

In recent years, silica nanoparticles (SiNPs) have attracted considerable attention as drug delivery platforms, particularly in oncological research. The present study describes the synthesis of SiNPs and their surface functionalization with amino and phosphate groups (SiNPs-NH 2 -PO 3 ). The modified nanoparticles were loaded with the anticancer drug daunorubicin (SiNPs-NH 2 -PO 3 -DNR) and subsequently modified with PEG2000, PEG4000, citric acid, or bovine serum albumin to evaluate the influence of surface ligands on nanoparticle size and zeta potential. Based on their physicochemical properties, the formulations SiNPs-NH 2 -PO 3 -DNR and SiNPs-NH 2 -PO 3 -DNR-PEG2000 were selected for detailed characterization. In vitro cytotoxicity was evaluated in MCF7 breast cancer cells, together with the potential induction of apoptosis using immunofluorescence markers, including active caspase-7, cleaved poly(ADP-ribose) polymerase (PARP), and p53 protein. Daunorubicin release was enhanced under mildly acidic conditions (pH 5.0), consistent with the pH-responsive behavior of the developed formulations. In contrast, SiNPs-NH 2 -PO 3 -DNR and SiNPs-NH 2 -PO 3 -DNR-PEG2000 exhibited lower cytotoxicity at physiological pH (7.4) in the MCF7 in vitro model. The data support pH-dependent activation of the formulations in MCF7 in vitro model. These findings support the proof-of-concept potential of the developed nanoparticles as pH-responsive drug delivery systems and demonstrate controlled daunorubicin release under acidic conditions in vitro.