Cancer‐Targeted Nanomedicine: Overcoming the Barrier of the Protein Corona

Nanomedicines exploit the unusual physicochemical and biological properties of nanoparticles, including their nanoscopic size, high surface‐area‐to‐volume ratio, easy surface modification, and biocompatibility. Among various therapeutic and diagnostic applications of nanomedicines, cancer‐targeted drug delivery systems (DDS) have been found to be a promising area of research. Effective DDS rely on two major factors: slow and sustained release of chemotherapeutic drugs and their targeted delivery to tumor sites. Both the drug release and targeting ability of nanoparticles are greatly affected under in vivo conditions by the “protein corona,” a tightly packed layer of protein molecules, formed around nanoparticles upon contact with biological fluids. Owing to the adsorption of proteins onto the surface of nanoparticles, their identity is significantly altered, and they can readily be cleared from systemic circulation by the mononuclear phagocytic system. In this context, scientists have employed various strategies, including the use of different ligands, stealth polymers, and protein corona shields/pre‐coating with specific proteins to modulate protein corona formation and retain the targeting ability of nanoparticles. This review article focuses on the recent progress of these different strategies with a special emphasis on the protein corona shields/artificial protein corona approaches for the development of effective cancer targeting nanomedicines. Protein corona formation around nanoparticulate cancer drug delivery systems upon contact with biological fluid alters their identity, leading to subsequent rapid uptake by the mononuclear phagocytic system (MPS). This review describes the recent advances in different strategies, with a major focus on protein corona shields/artificial protein corona approaches to avoid MPS uptake and retain the cancer targeting ability of nanomedicines.