PEGylation and Zwitterionization: Pros and Cons in the Renal Clearance and Tumor Targeting of Near-IR-Eniitting Gold Nanoparticles

摘要

PEGylation is the most common and successful surface modification for reducing nonspecific accumulation and prolonging the blood circulation of inorganic nanoparticles (NPs) so that they can effectively target tumors through the well-known enhanced permeability and retention (EPR) effect. These strengths fundamentally arise from the fact that poly(ethylene glycol) (PEG) moieties on the particle surface create steric hindrance for serum protein (opsonin) adsorption and slow down NP uptake by the reticuloendothelial system (RES) organs, such as the liver and spleen. However, the majority of PEGylated NPs still end up in the RES organs after circulation, thus resulting in low targeting specificity (defined as the amount of NPs in the tumor versus that in the liver). For instance, even though PEGylated AuNPs with a 2 nm core size can circulate in the body at a high concentration, they were found to significantly accumulate in the liver (78% ID g~(-1); ID = injected dose) and spleen (15.2% ID g~(-1)) at 24 h post injection (p.i.). Such long-term severe accumulation in the RES potentially induces health hazards, thus hampering the clinical translation of NPs. Therefore, developing PEGylated inorganic NPs that not only retain a strong EPR effect but can also be eliminated from the urinary system like clinically used small-molecule contrast agents is highly desired but remains a big challenge.