Incorporation of nanoparticles in serum containing-media leads to spontaneous adsorption of proteins on the nanoparticle surface thus forming “protein corona”. The current study focuses on the variation in corona formation across differently functionalized (CTAB, SDS and Brij-58) SeNPs surfaces and the application of these coronated-SeNPs as reservoirs for holding positively charged doxorubicin (dox). Protein quantification and densitometry study reveal that cationic SeNPs (CTAB-SeNPs) promotes maximum corona formation, and also has a higher affinity towards predominantly negatively charged serum albumin. Further, protein coronation had a significant impact on the mean hydrodynamic diameter of the functionalized SeNPs. Parameters such as surface functionalization, total adsorbed protein and bound albumin content determine the loading capacity and release of dox payload. Protein densitometry reveals, that CTAB-SeNPs has the highest amount of bound albumin which in turn aided in enhanced loading of dox on the cationic NPs. The coronated-nanocarriers were further subjected to different pH-trigger, wherein all the coronated SeNPs had an enhanced dox release at pH- 4.6. The study also highlights that protein corona helps in impeding the burst release of dox from the conjugated system. Additionally, payload leakage study suggests, that bound corona proteins help in retaining dox and prevents significant desorption of the therapeutic molecule over time. However, the presence of positively charged dox disrupts the stability of the bound corona proteins making them prone to leakage. Finally, the cellular toxicity of the functionalized NPs were assessed, wherein dox-loaded protein coronated SeNPs induced significant cell death. The feasibility of employing protein-coronated-SeNPs as a new mode of drug delivery has been highlighted in this study.