Nanoparticles are emerging as carriers in biological applications due to advances in their preparation, size control, surface modification and encapsulation capabilities. In addition, nanomaterials improve bioavailability by enhancing aqueous solubility of the guest molecule and increasing resistance time in the body. However, the delivery of guest molecules is still challenging due to the intrinsic characteristics of the guest molecule including large size and propensity to denature or degradation in the case of biomolecules and the encapsulation stability of the small guest molecules. Our group recently reported the preparation of self-cross-linked polymeric nanogels possessing surface functionalization capabilities. In this dissertation we employed the use of polymeric nanogels to explore and understand their guest encapsulation capabilities with both hydrophilic and hydrophobic molecules. We were able to encapsulate a protein in the hydrophobic core of the nanogels and recover is enzymatic activity upon release. Moreover the surface of these nanogels can be also decorated with surface exposed cysteine containing protein. We also reported a straightforward methodology for the preparation of tri-functionalized amine materials with high functional density.