Hybrid nanomaterials possess the properties of both organic and inorganic components and find applications in various fields of research and technology. In this study, aerosol photopolymerization is used in combination with thiol-ene chemistry to produce silver poly(thio-ether) hybrid nanospheres. In aerosol photopolymerization, a spray solution of monomers is atomized, forming a droplet aerosol, which then polymerizes, producing spherical polymer nanoparticles. To produce silver poly(thio-ether) hybrids, silver nanoparticles were introduced to the spray solution. Diverse methods of stabilization were used to produce stable dispersions of silver nanoparticles to prevent their agglomeration before the photopolymerization process. Successfully stabilized silver nanoparticle dispersion in the spray solution subsequently formed nanocomposites with non-agglomerated silver nanoparticles inside the polymer matrix. Nanocomposite particles were analyzed via scanning and transmission electron microscopy to study the degree of agglomeration of silver nanoparticles and their location inside the polymer spheres. The nanoparticle hybrids were then introduced onto various biofunctionalization reactions. A two-step bioconjugation process was developed involving the hybrid nanoparticles: (1) conjugation of (biotin)-maleimide to thiol-groups on the polymer network of the hybrids, and (2) biotin-streptavidin binding. The biofunctionalization with gold-nanoparticle-conjugates was carried out to confirm the reactivity of -SH groups on each conjugation step. Fluorescence-labeled biomolecules were conjugated to the spherical nanoparticle hybrids (applying the two-step bioconjugation process) verified by Fluorescence Spectroscopy and Fluorescence Microscopy. The presented research offers an effective method of synthesis of smart systems that can further be used in biosensors and various other biomedical applications.