The extensive use of semiconducting nanoparticles such as quantum dots in biomedical and industrial products can lead to their inadvertent release into the freshwater system. Natural exudates in the aquatic system comprising extracellular polymeric substance (EPS) and protein-rich metabolites can eventually adsorb onto the quantum dots (QDs) surface and form an eco-corona. The alterations in the physio-chemical and toxicological behavior of CdSe/ZnS QDs under the influence of eco-corona in the freshwater system have not been explored yet. In the present study, lake water medium conditioned with exudate secreted by Scenedesmus obliquus was utilized as an eco-corona forming matrix. The time-based evolution of the eco-corona on the differently charged CdSe/ZnS QDs was analyzed using transmission electron microscopy and dynamic light scattering. Aging of amine-QDs in algal exudate for 72 h showed enhanced aggregation (Mean Hydrodynamic Diameter- 1969 nm) as compared to carboxyl-QDs (1543 nm). Further, eco-coronation tends to impart an overall negative charge to the QDs. The fluorescence intensity of amine-QDs was quenched by 84% due to the accumulation of higher eco-corona. An integrative effect of surface charge and accumulated eco-corona layer influenced the Cd2+ ion leaching from the QDs. An enhancement in the algal cell viability treated with carboxyl - CdSe/ZnS (90%) and amine- CdSe/ZnS QDs (94%) aged for 72 h suggested that eco-corona can effectively mitigate the inherent toxicity of the QDs. The oxidative stress markers in the algal cells (LPO, SOD, and CAT) were in correlation with the cytotoxicity results. The algal photosynthetic efficiency depended on the deposition of eco-coronated QDs on the cell surface. Cellular uptake results indicated low Cd2+ concentration of nearly 13.9 and 11.5% for carboxyl- and amine- CdSe/ZnS QDs respectively. This suggests that eco-coronation directly influences the bioavailability of engineered nanoparticles. © 2020 Elsevier Ltd