We describe the design and optimization of an amphiphilic diblock copolymer and its use to provide surface functionalization of colloidal semiconductor nanoparticles (quantum dots, QDs). This polymer coating promotes hydrophilicity of the nanocrystals while providing numerous functional groups ideally suited for biofunctionalization of the QDs using copper-catalyzed azide alkyne Husigen 1,3-cyloaddition (i.e., cupper catalyzed “click” reaction). Copper ions are known to quench the fluorescence of QDs in solution. Thus effective shielding of the nanocrystal surface is essential to apply copper-catalyzed reactions to luminescent QDs without drastically quenching their emission. We have applied a strategy based on micellar encapsulation within poly(isoprene-block- ethylene oxide) diblock-copolymers (PI-b-PEO), where three critical factors promote and control the effectiveness of the shielding of copper ion penetration: 1) The excess of PI-b-PEO, 2) the size of PI-b-PEO and 3) insertion of an additional PS-shell grown via seeded emulsion polymerization (EP) reaction. Due to the amphiphilic character of the block-copolymer, this approach provides a shielding layer surrounding the particles, preventing metal ions from reaching the QD surfaces and maintaining high photoluminescence. The effective shielding allowed the use of copper-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) to hydrophilic and highly fluorescent QDs, opening up great possibilities for the bio functionalization of QDs.