Controlling the Stealth Effect of Nanocarriers through Understanding the Protein Corona

The past decade has seen a significant increase in interest in the use of polymeric nanocarriers in medical applications. In particular, when used as drug vectors in targeted delivery, nanocarriers could overcome many obstacles for drug therapy. Nevertheless, their application is still impeded by the complex composition of the blood proteins covering the particle surface, termed the protein corona. The protein corona complicates any prediction of cell interactions, biodistribution, and toxicity. In particular, the unspecific uptake of nanocarriers is a major obstacle in clinical studies. This Minireview provides an overview of what we currently know about the characteristics of the protein corona of nanocarriers, with a focus on surface functionalization that reduces unspecific uptake (the stealth effect). The ongoing improvement of nanocarriers to allow them to meet all the requirements necessary for successful application, including targeted delivery and stealth, are further discussed. Stealth shield: The use of nanocarriers in medical applications is complicated by the formation of a protein corona on the nanocarrier surface. This can influence interaction with cell membranes, and makes it difficult to predict cellular interactions, biodistribution, and toxicity. This Minireview provides an overview of what we know about the protein corona of nanocarriers, with a focus on surface functionalization to reduce unspecific uptake—termed the stealth effect.