Quantum dots (QDs) based fluorescent nanostructures with advanced optical performance and bioanalytical use required rational design and surface engineering of high quality QDs. In current work, one-step strategy was applied to synthesis ultrasmall sized CdTe/CdS Coresmall/shellthick QDs directly in hydrophilic phase with a tunable near-infrared emitting window compatible for tumor targeting and cancer cell imaging. More impressively, these brilliant QDs possessed near-infrared electrochemiluminescence immunosensing properties towards biomarkers. To build brighter and stable QD composites which have scalable size (QD number) and enhanced signal to noise ratio beyond single QD, we developed an organosilane micellization approach to incorporate single or multiple QDs into silica beads displaying a 90% preserved quantum yield relative to hydrophobic QDs and excellent stability in aqueous medium. By this manner, another cadmium-free and environmental friendly hydrophobic CuInS2/ZnS near-infrared emitting QDs was embedded into silica beads demonstrating a well preserved emission properties regarding the photoluminescent spectrum and quantum yield. These fluorescent beads showed minor cytotoxcity and great potential in targeted cancer cell imaging. The strategy is also applicable for hydrophobic assemblies such as QDs immobilized silica spheres with high packing density. This allows the water solubilization of fluorescent nanospheres with high quantum yield. One can use the assembly-silication-assembly circle to create fluorescent encoded nanospheres, noble metal and magnetic particles incorporated QDs@SiO2 multifunctional nanocomposites. Key words: Nano-engineering, silica nanobeads, CuInS2/ZnS QDs, fluorescence, CdTe/CdS Coresmall/shellthick QDs