Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy.

ABSTRACT: Achieving selective and durable inhibition of programmed death ligand 1 (PD-L1) in tumors for T cell activation remains a major challenge in immune checkpoint blockade therapy. We herein presented a set of clickable inhibitors for spatially confined PD-L1 degradation and radioimmunotherapy of cancer. Using metabolic glycan engineering click bioorthogonal chemistry, PD-L1 expressed on tumor cell membranes was labeled with highly active azide groups. This enables covalently binding of the clickable inhibitor with PD-L1 and subsequent PD-L1 degradation. A pH-activatable nanoparticle responding to extracellular acidic pH of tumor was subsequently used to deliver the clickable PD-L1 inhibitor into extracellular tumor microenvironment for depleting PD-L1 on the surface of tumor cell and macropha

SUBMITTER: Hou B 

PROVIDER: S-EPMC11567003 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature