Protein‐Precoated Surface of Metal‐Organic Framework Nanoparticles for Targeted Delivery

Abstract Metal‐organic framework (MOF) nanoparticles have recently emerged as a promising vehicle for drug delivery with high porosity and feasibility. However, employing a MOF‐based drug delivery system remains a challenge due to the difficulty in controlling interfaces of particles in a biological environment. In this paper, protein corona‐blocked Zr 6 ‐based MOF (PCN‐224) nanoparticles are presented for targeted cancer therapy with high efficiency. The unmodified PCN‐224 surface is precoated with glutathione transferase (GST)‐fused targetable affibody (GST‐Afb) proteins via simple mixing conjugations instead of chemical modifications that can induce the impairment of proteins. GST‐Afb proteins are shown to stably protect the surface of PCN‐224 particles in a specific orientation with GST adsorbed onto the porous surface and the GST‐linked Afb posed outward, minimizing the unwanted interfacial interactions of particles with external biological proteins. The Afb‐directed cell‐specific targeting ability of particles and consequent induction of cell death is demonstrated both in vitro and in vivo by using two kinds of Afb, which targets the surface membrane receptor, human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR). This study provides insight into the way of regulating the protein‐adhesive surface of MOF nanoparticles and designing a more effective MOF‐hosted targeted delivery system.