Targeted-nanotherapeutics (NP) have largely failed to translate clinically in showcasing improved disease-specific localization and associated drug delivery efficacy, stemming from a lack of insight into the influence, the type of targeting ligand/ligand density has on nano-bio interactions such as the serum protein corona formation that dictate NP fate in vivo [1]. We have previously developed a therapeutic nano-formulation with decreased adhesivity to blood and non-specific tumor tissue components while maintaining a strong cell surface receptor-specific binding affinity (termed DART nanoparticles) [2]. Recently, we demonstrated in vivo, the efficacy of paclitaxel-loaded DART nanoparticles directed to the cell surface receptor: fibroblast growth factor inducible 14 (Fn14), in primary as well as metastatic triplenegative breast cancer models [3]. In this present work, we investigated the impact of varying the Fn14- specific targeting moiety type- full-length monoclonal antibody (ITEM4 mAb) or fragment, antigen binding (ITEM4 Fab)- on DART NPs surface; On NP-Fn14 target-specificity and the subsequent cellular-uptake profiles by human glioma cell lines. We extensively examined the relationship between the targeting moiety type (ITEM4-mAb vs ITEM4-Fab) and the associated NP-ligand surface density on 1) Fn14 specific binding profiles and affinities 2) The resulting cellular-uptake rates on human glioma cell lines, and the influence of NP-serum protein corona formation on these processes