Polymeric nanomaterials (NM) with nonspherical morphologies have increasingly captured the spotlight in biomedical applications. Physical deformation of nanospheres (NS) represents a versatile technique for obtaining ellipsoidal NM (E-NM) that exhibit unique properties regarding their interactions with biological systems. Despite this technique's versatility and simplicity, the film's detailed composition and the parameters controlling the efficiency of the NS’s physical deformation still need to be clarified. Herein, we detailed a step-by-step formulation of a film composed of polyvinyl alcohol (PVA), and we investigated the impact of NS surface properties on the efficiency of the physical stretching. To reach those objectives, we designed two morphologies (NS and E-NM), and for each morphology, the surface composition was modified by using three different polysaccharides (chitosan, dextran, and hyaluronan). Physicochemical analysis revealed a connection between NS surface potential, their interaction with PVA, and the aspect ratio of ellipsoidal NM. Chitosan-coated E-NM had the highest aspect ratio ( = 4.9), which decreased to 2.4 with dextran and hyaluronan coatings. Isothermal titration calorimetry demonstrated strong interaction between PVA and chitosan but little interaction with dextran and hyaluronan. Finally, the impact of NM morphology and surface properties on phagocytosis showed that E-NM exhibited a reduced internalization by macrophages and reduced cytotoxicity compared to NS. Overall, in this study, we highlighted that the aspect ratio of E-NM is controlled by the strength of the interaction with PVA with the polysaccharide on the NS surface and revealed the role of NM morphology in reducing cytotoxicity and escaping internalization by macrophages.