Dual ligand-assisted assembly of metal-organic frameworks on upconversion nanoparticles for NIR photodynamic therapy against hypoxic tumors.

The hypoxic nature of tumor microenvironments significantly impedes the effectiveness of photodynamic therapy (PDT). To address this challenge, we constructed a pioneering nanohybrid by integrating upconversion nanoparticles (UCNPs) and metal-organic frameworks (MOFs) through a dual-ligand-assisted assembly approach. We functionalized UCNPs with polyvinyl pyrrolidone (PVP) and branched polyethylenimine (PEI), enabling the in situ growth of MOFs on multiple UCNP-conjugates. This nanohybrid, termed UCM, possesses a unique heterogeneous structure that facilitates effective energy transfer from UCNPs to MOFs, enhancing NIR-activated PDT. A distinguishing feature of UCMs is biocatalytically active MOFs, which provide them with a peroxidase-like capability. This characteristic allows UCMs to utilize the excess H 2 O 2 in the tumor microenvironment, ensuring continuous oxygen production essential for type II PDT. Our research indicates that UCMs not only amplify the efficacy of PDT but also address the therapeutic challenges in hypoxic tumor microenvironments by supplying in situ oxygen.