A new strategy, dendrimer bridging, is developed for simultaneous formation and functionalization of biocompatible and bioaccessible semiconductor box nanocrystalssa dendron box around each colloidal semiconductor nanocrystal. CdSe plain core or CdSe/ CdS core/shell nanocrystals coated by a monolayer of organic dendron ligands (dendron nanocrystals) with hydroxyl groups as the terminal were chosen as the starting systems because of their potential biocompatibility and proven stability. A generation-two (G2) amineterminated dendrimer was used as the cross-linking and functionalization reagent, which yielded much more stable cross-linked nanocrystals than the simple diamine or trisamine cross-linking reagents did. The chemical, thermal, and photochemical stability of the resulting amine-terminating box nanocrystals (amine box nanocrystals) formed by dendrimer bridging are comparable to that of the first generation box nanocrystals, achieved by ring-closing metathesis (RCM), that are not biocompatible and need to be further functionalized for bioapplications. As expected, the amine groups on the surface of the box nanocrystals provide versatile and reliable conjugation chemistry under mild conditions. Using one of the conjugation methods, biotin molecules were readily coupled onto the amine box nanocrystals. The biomedical applications of those superstable box nanocrystals were demonstrated by the quantitative and reproducible precipitation of the picomole amounts of avidin with the biotinylated box nanocrystals. Experimental results further revealed that the amine box nanocrystals and related derivatives are fully biocompatible to the tested system, have no detectable nonspecific binding, are extremely stable in the desired bioenvironment, and have no noticeable interference with the bioactivities. The exceptional thermal stability further warrants those biocompatible box nanocrystals to be employed in a large temperature range needed for certain applications, such as PCR.