2025: Photocatalytic Nanoscale Metal-Organic Frameworks for Proximity Labeling in Living Cells

• Xin Tang, Yunhao Li, Mowei Zhou and Pengfei Ji*

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, we describe 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. 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. We envision further application of PNPL in assisting the rational development of nanoparticle-based photodynamic therapeutics.

通过阐明纳米粒子在活细胞内的精确定位和生物分子相互作用，可以理解纳米粒子疗法和生物材料的机制。为此，尽管酶和小分子催化的邻近标记广泛应用于绘制相互作用网络，但人们长期以来一直在寻求能够以生物分子精度绘制纳米粒子胞内微环境的技术。本文，我们描述了一种利用光催化纳米粒子进行邻近标记 (PNPL) 的方法，该方法利用光催化产生的单线态氧，用生物素标记选择性地标记蛋白质的组氨酸侧链，以识别活细胞中纳米粒子-蛋白质的共定位。该技术确定了光催化纳米级金属有机骨架 (pnMOF) 对 HeLa 细胞中细胞膜和内质网的靶向性，并观察到其对活细胞中纳米粒子行为的普遍影响。我们展望 PNPL 在辅助基于纳米粒子的光动力疗法的合理开发方面的进一步应用。