In this study, we prepared biocompatible, water-soluble, superparamagnetic, manganese-doped, magnetism-engineered iron oxide (MnMEIO) nanocrystals with reactive moieties. This was achieved via a one-pot synthesis protocol by thermally decomposing metal acetylacetonate precursors in 2-pyrrolidone in the presence of polyethylene glycol diacid. Using carbodiimide, we achieved nanocrystals coupled with 9-aminoacridine and folic acid through 2,2′-(ethylenedioxy)-bis-ethylamine. The results suggest that the nanocrystals provide carboxyl functional groups as binding sites. Their surface modification and composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS), respectively. Using Mössbauer spectroscopy and a magnetometer, we have shown that these nanocrystals exhibit superparamagnetic behaviors. In addition, we have demonstrated that the nanocrystals were not significantly toxic, and hence are biocompatible.