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A number of procedures are currently available to encapsulate and solubilize hydrophobic semiconductor Quantum Dots (QDs) for biological applications. Most of these procedures are based on the use of small-molecule coordinating ligands, amphiphilic polymers, or amphiphilic lipids. However, it is still not clear how these different surface coating molecules affect the optical, colloidal, and chemical properties of the solubilized QDs. Here we report a systematic study to examine the effects of surface coating chemistry on the hydrodynamic size, fluorescence quantum yield, photostability, chemical stability, and biocompatibility of water-soluble QDs. The results indicate that quantum dots with the smallest hydrodynamic sizes are best prepared by direct ligand exchange with hydrophilic molecules, but the resulting particles are less stable than those encapsulated in amphiphilic polymers. For stability against chemical …