The effective phase transfer of hydrophobic nanocrystals synthesized in nonpolar solvents into polar solvents remains great challenge for their nanomedicinal applications. To resolve this issue, the exsiting strategies for phase transfer of nanocrystals in organic solvents use amphiphilic compounds or lipids as imperative moieties by ligand exchange and encapsulations. Ligand exchange involves by exchanging the hydrophobic molecules with bifunctional compounds and small size of molecules is coordinated with functional molecules to increase the steric repulsion forces between boundary of water and nanoparticles. However, the yield of phase transferred nanocrystals from hydrophobic nonpolar to hydrophilic polar phase is exceptionally low, and sometime irreversible desorption of replaced ligands leads to agglomeration and aggregation. Also, their intrinsic physiochemical properties are easily influenced by surrounding ion species or pH when the particles are suspended in phosphate saline buffer (PBS). Moreover, conjugation of bioactive molecules often leads to colloidal instability in PBS because of the hydrodynamic nature of the amphiphilic molecules on the surfaces of nanoparticles. Here we report a robust and simple post-synthetic surface modification procedure of hydrophobic nanoparticles to remove the original surface-bound carboxylic acid and increase the water-solubility for nanomedicinal applications.