This work systematically describes one-step synthesis of hydrophilic functionalized superparamagnetic iron oxide nanoparticles (SPIONs) via thermolysis in presence of polyamines such as diethylene triamine (DETA), triethylene tetraamine (TETA), tetraethylene pentamine (TTEPA), or pentaethylene hexamine (PEHA) or mixture of a polyamine (TETA) and polyols such as diethylene glycol (DEG), triethylene glycol (TEG) or tetraethylene glycol (TTEG) while varying the polyamine: polyol (v/v) ratio, reaction temperature and reaction time. The saturation magnetization (Ms) values of the as-prepared polyamine (DETA/TETA/TTEPA/PEHA) coated SPIONs are determined in the range of 31.8–48.5 emu/g, which is altered in the range of 40.2–57.8 emu/g by the addition of a polyol (DEG/TEG/TTEG) to the polyamine (TETA) at different ratios. Moreover, the Ms. values are further improved to 64.6 and 66.8 emu/g at the optimized TETA:TEG (1:1) ratio by prolonging the reaction time up-to 2 h and the reaction temperature to 270 °C, respectively. In addition, the TETA-TEG coated SPIONs have displayed their average particle sizes, hydrodynamic sizes, and zeta potential (ζ) values in the range of 7–11 nm, 99–120 nm and +45 to +57 mV, respectively (indicating high water solubility). Finally, the TETA-TEG coated SPIONs with the highest Ms. and ζ values (i.e. 66.8 emu/g and +57 mV) are selected for the biological studies, where they have revealed excellent (i) cytocompatibility, and (ii) intracellular uptake in the cancer (HepG2 liver & MCF-7 breast) cells for the incubation periods of 24/48 h. Thus, the TETA-TEG coated SPIONs based aqueous ferrofluids have a great potential to be used in biomedical applications. © 2018 Elsevier B.V.