ABSTRACT
Zwitterionic molecules are known to resist nonspecific protein adsorption and have been proposed as an alternative to the widely used polyethylene glycol. Recently, zwitterionic-like nanoparticles were created from the coimmobilization of positive and negative ligands, resulting in surfaces that also prevent protein corona formation while keeping available sites for bioconjugation. However, it is unclear if they are able to keep their original properties when immersed in biological environments while retaining a toxicity-free profile, indispensable features before considering these structures for clinics. Herein, we obtained optimized zwitterionic-like silica nanoparticles from the functionalization with varying ratios of THPMP and DETAPTMS organosilanes and investigated their behavior in realistic biological milieu. The generated zwitterionic-like particle was able to resist single-protein adsorption, while the interaction with a myriad of serum proteins led to significant loss of colloidal stability. Moreover, the zwitterionic particles presented poor hemocompatibility, causing considerable disruption of red blood cells. Our findings suggest that the exposure of ionic groups allows these structures to directly engage with the environment and that electrostatic neutrality is not enough to grant low-fouling and stealth properties.
ABSTRACT
Protein coronas form on the surfaces of nanomaterials in biological fluids. This layer of proteins affects the properties of nanomaterials, altering their behavior and masking engineered functionality. The use of nonfouling moieties reduces or prevents corona formation; however, these ligands typically complicate functionalization. We present here a surface modification strategy for silica nanoparticles using specific molar ratios of zwitterionic and amine moieties. Through proper balance of ligands, we were able to generate particles that featured reactive "handles", while retaining nonfouling properties, high hemocompatibility, and low cytotoxicity.
