On the cellular selectivity of targeting peptide-nanoparticle conjugates – a nanoparticle perspective

Peptide-targeted nanoparticles are promising drug carriers that can enhance drug efficacy at low systemic doses. However, clinical applications are compromised by off-target effects. Nanoparticle surface chemistry fine-tuning is key for solving these problems. The literature related to peptide-based, active targeting is reviewed, and critically discussed, with focus on the influence of surface chemistry influences on targetability. Furthermore, issues related to limited in vitro–in vivo predictivity are discussed. The potential of more advanced in vitro methods for an increased in vivo prediction is discussed in combination with advanced computational approaches. Efforts toward enhancing endosomal escape are identified as key future developments, in combination with decreasing off-target effects.