Electrostatic self-assembly of PEG copolymers onto porous silica nanoparticles.

A critical requirement toward the clinical use of nanocarriers in drug delivery applications is the development of optimal biointerfacial engineering procedures designed to resist biologically nonspecific adsorption events. Minimization of opsonization increases blood residence time and improves the ability to target solid tumors. We report the electrostatic self-assembly of polyethyleneimine-polyethylene glycol (PEI-PEG) copolymers onto porous silica nanoparticles. PEI-PEG copolymers were synthesized and their adsorption by self-assembly onto silica surfaces were investigated to achieve a better understanding of structure-activity relationships. Quartz-crystal microbalance (QCM) study confirmed the rapid and stable adsorption of the copolymers onto silica-coated QCM sensors driven by strong electrostatic interactions. XPS and FT-IR spectroscopy were used to analyze the coated surfaces, which indicated the presence of dense PEG layers on the silica nanoparticles. Dynamic light scattering was used to optimize the coating procedure. Monodisperse dispersions of the PEGylated nanoparticles were obtained in high yields and the thin PEG layers provided excellent colloidal stability. In vitro protein adsorption tests using 5% serum demonstrated the ability of the self-assembled copolymer layers to resist biologically nonspecific fouling and to prevent aggregation of the nanoparticles in physiological environments. These results demonstrate that the electrostatic self-assembly of PEG copolymers onto silica nanoparticles used as drug nanocarriers is a robust and efficient procedure, providing excellent control of their biointerfacial properties.