Modular Nanoparticles for Selective Cell Targeting

Nanoparticles (NPs) are an emerging technology in biomedical engineering with opportunities in diagnostics, imaging, and drug delivery. NPs can be prepared from a wide range of organic and/or inorganic materials. They can be fabricated to exhibit different characteristics for biomedical applications. The goal of this thesis was to develop NPs with tunable surface properties for selective cell targeting. Specifically, polyelectrolyte complexes composed of heparin (Hep, a growth factor binding glycosaminoglycan) and poly-L-lysine (PLL, a homopolymeric lysine) were prepared via a pulse sonication method. The Hep/PLL core NPs were further layered with additional Hep, tetrazine (Tz) modified Hep, or dextran sulfate (DS). The addition of Tz handle on Hep backbone permitted easy modification of NP surface with norbornene (NB) modified motifs/ligands, including inert poly(ethylene glycol) (PEG), cell adhesive peptides (e.g., RGD), and/or fluorescent marker. Both Hep and DS coated NPs could be readily internalized by J774A.1 monocytes/macrophages, whereas PEGylated NPs effectively reduced cellular uptake/recognition. The versatility of this NP system was further demonstrated by laying DS on the Hep/PLL NP surface. DS-coated NPs were recognized by J774A.1 cells more effectively. Furthermore, DS-layered NPs seemed to reduce IL-10 production on a per cell basis, suggesting that these NPs could be used to alter polarization of macrophages.