Nanoparticle-mediated targeting chimeras transform targeted protein degradation

Recent findings indicate that nanoparticles (NPs) can mediate targeted protein degradation (TPD) with versatility and efficiency. Studies have shown that ligand-modified NPs can effectively degrade both extracellular and intracellular proteins of interest through an autolysosome-involved degradation pathway, independent of both NPs and ligand types. This phenomenon, where ligand-modified NPs shuttle proteins of interest towards degradation, may prompt researchers to rethink the design of ligand-NPs, incorporating TPD as an additional functionality beyond conventional delivery. Moreover, this approach has the potential to revolutionize the field of TPD by transitioning from labour-intensive, case-specific designs to a broadly adaptable 'plug-and-play' platform that makes full use of the in vivo delivery potential of NPs. This Perspective discusses the evolution of current TPD tools, the desired features of next-generation technologies, and the potential and challenges of NP-mediated targeting chimeras for TPD, highlighting emerging trends and raising awareness of this promising field.