In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organoruthenium complex, [Ru(ppy-CHO)(phen) 2 ][PF 6 ] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex. 47 example, the ruthenium(III) complex NKP-1339 is undergoing 48 clinical trials for cancer treatment, 11 and Ru II (η 6 -arene) 49 complexes have been investigated for their tunability and 50 novel modes of action. 12−15 The combination of polypyridyl 51 ruthenium drugs with nanoscale drug delivery systems has 52 garnered a great deal of research attention. 16,17 Compared with 53 the planar structure of platinum drugs, the octahedral 54 configuration of ruthenium complexes provides a rigid 55 framework for the construction of a nanocarrier and their 56 planar ligands may provide hydrophobic cavities for drug 57 loading. 18 However, many Ru complexes have limited capacity 58 to cross the cell membrane. 19,20 59 Mesoporous silica nanoparticles (MSNs) have unique 60 properties such as a large surface area, high stability and 61 degree of tunability, and good biocompatibility, making them 62 excellent vehicles for the delivery of any type of drug, especially 63 one with antitumor purposes. 21 Other materials widely used in 64 drug delivery are liposomes and polymeric nanoparticles. 65 Unlike the first ones with low stability or the second ones