Ensuring colloidal stability of cisplatin-loaded mesoporous silica nanoparticles: from synthesis to cytotoxicity...

Mesoporous silica nanoparticles (MSNs) have attracted significant attention as a promising drug delivery platform for cancer treatment. However, their colloidal stability often remains overlooked, despite the numerous drawbacks associated with its absence. In this study, the enhancement of the colloidal stability of thoroughly characterised (TEM, DLS, zeta potential, TGA, XRD, N₂ physisorption) monodisperse MCM-41 MSNs in physiological conditions through the grafting a comb-like copolymer was successfully accomplished (preservation of the hydrodynamic diameter and the polydispersity index for at least 3 days). The loading of a therapeutic agent, cisplatin, was then achieved (12 wt%) without compromising their colloidal stability, and drug release kinetics were evaluated in cell culture medium, observing a complete release of the cargo after 48 h. Cytotoxicity studies conducted before and after drug loading confirmed the innocuousness of unloaded MSNs and demonstrated cytotoxic effects comparable to those of free cisplatin for the loaded nanoparticles (IC₅₀ = 23 and 13 μM CDDP for loaded MSNs versus 24 and 11 μM CDDP for free cisplatin in, respectively, SW480 and A549 cell lines). Particular emphasis was placed on ensuring the reproducibility of the results (e.g., hydrodynamic diameter and polydispersity index were measured across 49 independent synthesis) and on thoroughly evaluating the colloidal stability of the nanoparticles throughout the study, from synthesis to cytotoxicity assays. To the best of our knowledge, this work represents the first systematic study of the conditions required to develop stable colloidal suspensions of monodispersed mesoporous silica nanoparticles loaded with cisplatin, achieving high reproducibility, which constitutes a novel and robust contribution to the field.