Photocatalytic Nanoscale Metal‐Organic Frameworks for Proximity Labeling in Living Cells

The behavior of nanoparticles in living cells has always been challenging to figure out. This work employs PCN-224 (a nanoparticle for photodynamic therapy) to establish Photocatalytic Nanoparticles for Proximity Labeling (PNPL) strategy for detecting the targets and influencing effects of nanoparticles in living cells, demonstrating the potential of this strategy to be applied to the development of nanotherapeutics.

Abstract

The mechanism of nanoparticle-based therapeutics and biomaterials can be understood through the elucidation of their precise localization and biomolecular interactions within living cells. To this end, although proximity labeling catalyzed by enzymes and small molecules are broadly applied for mapping interaction networks, technologies that can map the intracellular microenvironments of nanoparticles with biomolecular precision have long been sought. Here, an approach that uses photocatalytic nanoparticles for proximity labeling (PNPL) that exploits photocatalytic generation of singlet oxygen to selectively label histidine side chains of proteins with a biotin tag to identify nanoparticle-protein co-localization in living cells is described. This technique identified the targeting of a photocatalytic nanoscale metal-organic framework (pnMOF) toward cell membrane and endoplasmic reticulum in HeLa cells, and observed generalizable effects on the behavior of nanoparticles in living cells. Further application of PNPL in assisting the rational development of nanoparticle-based photodynamic therapeutics is envisioned.