PD-L1-targeted polymer-peptide-immune nanomedicine synergizes radiotherapy for durable tumor control.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40496627.
- Also identified by DOI 10.1016/j.bioactmat.2025.05.017 and PMC identifier 12148823.
- Licence recorded as CC BY-NC-ND.
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Abstract
Radiotherapy (RT) is a cornerstone of cancer treatment but limited by its dual role in modulating the tumor immune microenvironment: while promoting immunogenic cell death (ICD), RT concurrently upregulates PD-L1 to suppress antitumor immunity. To address this limitation, we developed PEP-PLG-IMDQ, a polymer-peptide-immune agonist nanomedicine that synergizes RT with immunotherapy. This nanoplatform employs a poly (<sub>L</sub>-glutamic acid) carrier conjugated with a PD-L1-targeting peptide and the TLR7/8 agonist imidazoquinoline (IMDQ), enabling three-pronged action: (1) PD-L1-mediated tumor targeting, (2) TLR7/8-driven dendritic cell activation, and (3) reinforcement of the anti-tumor immune cycle. In CT26 tumor-bearing mice, RT combined with PEP-PLG-IMDQ achieved 98.1 % tumor suppression, with 83 % long-term survival and complete resistance to tumor rechallenge. Mechanistically, the combination therapy enhanced CD8<sup>+</sup> T cell infiltration (5.3-fold vs. RT alone) and established durable immune memory. Our work provides a translatable strategy to overcome radioresistance through spatiotemporal immune modulation.