Porphyrin-based metal–organic framework nanocrystals for combination of immune and sonodynamic therapy

Immune therapy based on programmed death-ligand 1 (PD-L1) is widely used to treat human tumors. The current strategies to improve immune checkpoint blockade therapy fail in rescuing increased expression of PD-L1 in tumor issues. Here, we for the first time synthesized the metal–organic framework (MOF) nanocrystals of rare-earth element dysprosium (Dy) coordinated with tetrakis(4-carboxyphenyl) porphyrin (TCPP), which show well-defined two-dimensional morphologies. The MOF nanocrystals of Dy-TCPP could apparently reduce PD-L1 expression in tumor cells both in vitro and in vivo, and therefore display effective tumor treatment through immune therapy without any immune checkpoint inhibitor drugs. Considering the sensitivity of TCPP ligand toward ultrasound, the prepared Dy-TCPP can also realize sonodynamic therapy (SDT) besides immune therapy. In addition, the Dy-TCPP nanocrystals can efficiently obtain T₂-weight magnetic resonance imaging (MRI) of tumor sites. Our study provides the Dy-TCPP nanocrystals as promising diagnostic MRI-guided platforms for the combined treatment on tumors with SDT and immune therapy. Moreover, this strategy succeeds in reducing the elevated expression of PD-L1 in tumor cells, which might serve as a novel avenue for tumor immunotherapy in future.