A multifunctional nanoplatform capable of dual action on tumor PD-L1 for enhanced cancer theranostics

Due to the large amount of PD-L1 on the surface of tumor cells, antibody drugs can only block a small part of PDL1, limiting the effectiveness of immunotherapy. Here, a MnS nanocluster grafted with dimeric PD-L1 affibody (ZPD-L1) was developed to double act on PD-L1 of tumor cells. ZPD-L1 can specifically target PD-L1 on the surface of tumor cells, and block the interaction between PD-1 and PD-L1 to a certain extent. In acidic tumor microenvironment, MnS nanoclusters can release Mn2+ and H2S. The released Mn2+ can induce reactive oxygen species (ROS) generation through Fenton-like reaction, and serve as magnetic resonance imaging (MRI) contrast agent for effective therapeutic monitoring. H2S can down-regulate PD-L1 expression of tumor cells by amplifying ROS production to inhibit ATP level. Based on ZPD-L1-mediated PD-1/PD-L1 blocking and ROS-induced downregulation of PD-L1 expression, MnS nanoclusters can achieve dual action on tumor PD-L1, amplify immunogenic cell death, maximize the activation of anti-tumor immune response and inhibit tumor growth.