Electrostatic Self-Assembly of PEG Copolymers onto Porous Silica Nanoparticles

Abstract

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.

Surface functionalized mesoporous silica nanoparticles as an effective carrier for epirubicin delivery to cancer cells

“…It has been shown that introduction of PEI into PEG can improve particle size and dispersion of nanoparticles [26,[43][44][45][46]. In the present study, we incorporated PEI 1.8 kDa, which is not toxic to cells [47,48], to the surface structure of MSNs.…”

Synthesis of a novel zwitterionic biodegradable poly (α,β-l-aspartic acid) derivative with some l-histidine side-residues and its resistance to non-specific protein adsorption

“…The protein adsorption may induce adverse bioresponses, including complement activation, coagulation and thrombosis, or other undesirable biophysical and biochemical processes [1][2][3]. For example, liposomes, vehicles, micelles and polymeric nanoparticles have been widely used as nanocarrier systems for targeted delivery [4,5], but the size increase and serious particle agglomeration leaded by adsorbing protein C3b, fibrinogen or immunoglobulins G, may resulting in rapid clearance from blood circulation and concentration in liver and spleen and severely compromising drug delivery to the target tissue [1,[6][7][8]. The fibrinogen-cell interaction subsequently promotes thrombin, and coagulation cascade [9].…”

Silica-Based Nanoparticles for Intracellular Drug Delivery

“…However, the electrostatic forces that govern the physical adsorption of biocompatible macromolecules are often the most simple and efficient method for immobilization. Many macromolecules, such as PEG, proteins or lipids can be physically adsorbed onto nanoparticles surface to decorate them with a variety of functional groups (Van Shooneveld et al 2008;Thierry et al 2008).…”