Cross-Linked Poly(ethylene glycol) Shells for Nanoparticles: Enhanced Stealth Effect and Colloidal Stability

Preventing protein corona formation and macrophage uptake is the key to improving the delivery efficiency of nanocarriers. Herein, we present a kind of cross-linking poly(ethylene glycol) (CL-PEG) shell-wrapped gold nanoparticles (namely, Au@CL-PEG NPs), which show much enhanced stealth effect and colloidal stability in physiological environments. Compared to the AuNPs coated with conventional linear PEGs (namely, Au@PEG NPs), Au@CL-PEG NPs have a greater ability to resist protein adsorption and thus show reduced cellular uptake by macrophages. In addition, the Au@CL-PEG NPs show higher chemical and colloidal stability under different extreme conditions than the conventional Au@PEG NPs. The CL-PEGylation strategy provides a new window for the surface functionalization of nanomaterials, indicating great promise for the development of high-performance nanomedicines.