The surface charge of the plasma membrane (PM) and the large salt content of the extracellular space ensure a significant role of the electrostatic effect dictating the interaction between the PM and an approaching nanoparticle (NP). In this article, we theoretically study the case of an ionizable silica NP approaching the PM. We witness that the surface charge of the silica NP, dictated by the surface ionization of the charge In other words, a silica NP is more negative away from the PM than close proximity to the PM. Accordingly, we witness a significantly lower repulsion between the PM and NP favoring the approach and the interactions of the silica NP with the PM. Additionally, the presence of the silica NP in the vicinity of the PM induces a large nonisopotentiality, even silica in the electrostatic environment created by the PM surface and the extracellular ion concentration, decreases as it approaches the across a fully permeable PM. We anticipate that these findings will be critically important in the better design of the widely used silica NPs for targeted drug and gene deliveries.