LAUSR

Nanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off‐target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. These key surface properties—bioinert and stealth versus interactive at the target site—are in contradiction to each other so that the best compromise between them has to be found. Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. Stimuli‐responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.