Encapsulating metal nanoclusters inside porous organic cage towards enhanced radio-sensitivity and solubility

Abstract Metal nanoclusters are promising candidates for clinical applications such as radiation-enhanced therapy. However, the high surface energy generated by nanoscale size inevitably results into sever aggregation and poor biocompatibility. Herein, we report Pt nanoclusters encapsulated in soluble porous organic cages which contains accessible and discrete cavities (Pt-in-(HR)CC3). Unlike chemical protection that may perturb the size distribution and reduce the performance of nanoclusters, the physical confinement endows Pt-in-(HR)CC3 with homogenous distribution of Pt nanoclusters (~1.7 nm) and enhanced solubility. Moreover, Pt-in-(HR)CC3 demonstrates low toxicity and superior performance in radiotherapy sensitization for both short-term and long-term anti-cancer effects. Mechanism studies reveal that Pt-in-(HR)CC3 could facilitate the generation of reactive oxygen species, inhibition of cancer cell migration, and induction of cancer cell apoptosis. The strategy provides a general idea to joint biomedical areas with sophisticated materials chemistry.